The DOI matches its Crossref record; 196 of the 196 references it cites were found in a registry or an index; 12 of the 233 sources its claims cite were checked for support.
Metformin: an old but still the best treatment for type 2 diabetes
Open accessAbstract
The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin's mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin's negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection.
Overview
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Written from the paper’s full text.
TL;DR
This narrative review argues that metformin remains the first-line oral agent for type 2 diabetes because of its glycemic efficacy, safety profile, and benefits extending beyond glucose lowering (vascular, inflammatory, oxidative, and possible anticancer and neuroprotective effects). It surveys evidence across pre-diabetes, combination therapy, pregnancy, pediatrics, obesity/NAFLD, heart failure, HIV lipodystrophy, cancer, and contraindications.
Key findings
- In the Diabetes Prevention Program (DPP), lifestyle intervention and metformin reduced diabetes incidence by 58% and 31% respectively versus placebo; after a 1–2 week washout, metformin still significantly reduced incidence (risk ratio 0.75, p = 0.005), with benefit concentrated in patients <60 years (RR 0.66) and BMI >35 kg/m² (RR 0.47).
- In the UKPDS, the metformin-treated group had risk reductions of 32% (p = 0.002) for any diabetes-related endpoint, 42% for diabetes-related death (p = 0.017), and 36% for all-cause mortality (p = 0.011) versus control; post-trial follow-up showed persistent reductions for any diabetes-related endpoint (21%, p = 0.01), myocardial infarction (33%, p = 0.005), and death from any cause (27%, p = 0.002).
- Observational studies report reduced cancer incidence and cancer-related mortality in metformin users, consistently in the range of 25% to 30%; one cohort found cancer incidence of 7.3% in metformin users versus 11.6% in controls (unadjusted hazard ratio 0.46, 95% CI 0.40–0.53).
- Reported lactic acidosis incidence is 6.3 per 100,000 patient-years with metformin versus 40–64 per 100,000 patient-years with biguanides (mostly phenformin); gastrointestinal intolerance occurs frequently, and about 10–30% of patients show reduced vitamin B12 absorption.
Methods
- Narrative (non-systematic) review of the literature on metformin in type 2 diabetes, covering its mechanism (LKB-1/AMPK activation, reduced hepatic glucose output, mitochondrial respiration inhibition), clinical trials, and observational studies.
- Evidence summarized includes major randomized trials (DPP, DPPOS, IDPP, UKPDS, ADOPT, MiG, HOME, PRESTO), meta-analyses, and retrospective/observational cohorts, presented in narrative form plus two summary tables (diabetes prevention and vasculoprotection).
- No stated search strategy, inclusion criteria, or formal quality appraisal is described.
Limitations
- Stated in the paper: a meta-analysis suggesting smaller cardiovascular effects of metformin "must be interpreted with caution given the low number of randomized controlled trials included"; epidemiological comparisons of sulfonylureas versus metformin "are potentially affected by unmeasured confounding variables"; pediatric studies are few, of short duration, and heterogeneous in design; the effect of metformin on endothelial function is contradictory across studies and requires further study; whether increased cancer mortality with sulfonylureas/insulin reflects harm from those agents or protection from metformin "is not known."
- Evident from the text: as a narrative review without a described systematic search or quality assessment, selection and interpretation of cited evidence may be subject to bias; several key claims (cancer, neuroprotection, heart failure safety) rest largely on observational or in vitro/in vivo data rather than randomized trials.
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Claims the paper makes
165 Not checked yet · 7 Own interpretation · 3 Supported · 2 Partly supported · 1 Supported so far · 1 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Diabetes incidence rates were similar between treatment groups: 5.9 per 100 person-years (5.1–6.8) for lifestyle, 4.9 (4.2–5.7) for metformin, and 5.6 (4.8–6.5) for placebo.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Supportedcites [11] Diabetes Prevention Program Research Group: 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009, 374 (9702): 1677-1686. 10.1016/S0140-6736(09)61457-4. source
The Abstract Findings report that diabetes incidence rates during DPPOS were similar between treatment groups and give exactly 5.9, 4.9, and 5.6 cases per 100 person-years for lifestyle, metformin, and placebo, respectively. The Results also state that rates did not significantly differ between groups during DPPOS. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In this study, treatment of bovine capillary endothelial cells incubated in hyperglycemic medium with metformin was able to decrease the activity of NF-kB and others intracellular proteins related to cellular metabolic memory.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on oxidative stress
What the sources say
- Supportedcites [103] Zheng Z, Chen H, Li J, Li T, Zheng B, Zheng Y, Jin H, He Y, Gu Q, Xun X: Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin. Diabetes. 2012, 61 (1): 217-228. 10.2337/db11-0416. source
The Results section on bovine retinal capillary endothelial cells reports that metformin attenuated the high-glucose-induced increase in NF-κB, Bax, and PAR protein expression. This supports the claimed effect on proteins associated with metabolic memory, although the cellular result is described as reduced expression rather than a direct measurement of NF-κB activity. No page number is available in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“It has also direct effects on fibrin structure and function by decreasing factor XIII activity and changing fibrin structure [92].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on hemostasis
What the sources say
- Supportedcites [92] Standeven KF, Ariens RA, Whitaker P: The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Diabetes. 2002, 51: 189-197. source
The ‘Effect of DMB on FXIII activity in vitro’ section reports that metformin decreased FXIII cross-linking activity. The clot-structure results report significantly thinner fibrin fibers and smaller pores in clots formed with metformin. These experiments support the attributed direct effects on fibrin formation, without implying that metformin binds directly to FXIII. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The reduced risk of cancer and cancer mortality observed in these studies has been consistently in the range of 25% to 30% [135-139,145-147].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Partly supportedcites [135] Li D, Yeung SJ, Hassan MM, Konopleva M, Abbruzzese JL: Anti-diabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009, 137 (2): 482-488. 10.1053/j.gastro.2009.04.013. sourceExperimental — accuracy not yet measured
The Results report lower pancreatic-cancer risk among metformin users with diabetes, but the reported odds ratio of 0.38 corresponds to a 62% reduction in odds, not 25%–30%. The paper does not report cancer mortality or establish a consistent reduction across studies. (LLM, conf=0.87)
- Not checked yetcites [136] Donadon V, Balbi M, Valent F, Avogaro A: Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenterol. 2010, 16 (24): 3025-3032. 10.3748/wjg.v16.i24.3025. source
- Partly supportedcites [137] Libby G, Donnelly LA, Donnan PT: New users of metformin area at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009, 32: 1620-1625. 10.2337/dc08-2175. sourceExperimental — accuracy not yet measured
The Results (Main outcome measures and Secondary outcomes; page unavailable) report lower cancer incidence and cancer mortality among metformin users than comparators, both with an adjusted hazard ratio of 0.63—a 37% reduction. The paper therefore supports the direction of the claim, but not its stated 25%–30% range or the assertion that findings across studies were consistently in that range. (LLM, conf=0.88)
- Partly supportedcites [138] Landman GW, Kleefstra N, van Hateren KJ: Metformin associated with lower cancer mortality in type 2 diabetes ZODIAC-16. Diabetes Care. 2010, 33: 322-326. 10.2337/dc09-1380. sourceExperimental — accuracy not yet measured
The Results (Cancer mortality) support an association between metformin use and lower cancer mortality. But the adjusted hazard ratio is 0.43, corresponding to an estimated 57% reduction—not the claimed 25%–30%. This study measured cancer mortality rather than cancer incidence. (LLM, conf=0.88)
- Could not verifycites [139] Lee JH, Kim TI, Jeon SM: The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer. 2011, 12: 1-24. sourceExperimental — accuracy not yet measured
The Methods and Results describe a comparison of laparoscopic and open surgery for ovarian metastases from gastric cancer, not studies of metformin users. A search of our copy for metformin, cancer risk, and cancer mortality found no passage reporting a 25%–30% reduction; the Discussion’s 30% figure is a two-year survival rate after metastasectomy. (LLM, conf=0.77)
- Partly supportedcites [145] Evans J, Donelly L, Emslie A: Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005, 330 (7503): 1304-1305. 10.1136/bmj.38415.708634.F7. sourceExperimental — accuracy not yet measured
The table in the Comment section reports adjusted odds ratios of 0.75 and 0.73 for two metformin-prescription categories, consistent with roughly 25%–27% lower odds of cancer. But this pilot case-control study reports other estimates outside the claimed range, does not assess cancer mortality, and cannot establish consistency across the other cited studies. Page numbers are not available in our copy. (LLM, conf=0.87)
- Partly supportedcites [146] Bodmer M, Meier C, Krähenbühl S: Long-term metformin Use is associated with decreased risk of breast cancer. Diabetes Care. 2010, 33: 1304-1308. 10.2337/dc09-1791. sourceExperimental — accuracy not yet measured
The Conclusions report a 27% lower overall cancer risk in one earlier study (adjusted OR 0.73), which falls within the claimed range. But the paper’s own Results report a 37% lower breast cancer risk for users with ≥30 prescriptions (OR 0.63) and a 56% lower risk with ≥40 prescriptions (OR 0.44). Its discussion of cancer mortality gives no 25–30% estimate, so this source does not support the claim that the reductions were consistently in that range. (LLM, conf=0.86)
- Partly supportedcites [147] Bowker SL, Majumdar SR, Veugelers P, Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who usesulfonylureas or insulin. Diabetes Care. 2006, 29: 254-258. 10.2337/diacare.29.02.06.dc05-1558. sourceExperimental — accuracy not yet measured
The Results report cancer-related mortality of 3.5% in metformin users versus 4.9% in sulfonylurea users, an approximately 29% lower unadjusted proportion. The paper did not measure cancer incidence; its introduction reports a 23% reduction in another study, so this source does not establish that reductions in both cancer risk and mortality were consistently 25%–30% across studies. The authors also say it is uncertain whether the mortality difference reflects a protective effect of metformin. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Structural and pharmacokinetic differences in metformin such as poor adherence to the mitochondrial membrane, lack of interference with lactate turnover, unchanged excretion, and inhibition of electron transport and glucose oxidation may account for such differences [161].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin contraindications
What the sources say
- Partly supportedcites [161] Tahrani AA, Varghese GI, Scarpello JH, Hanna FWF: Metformin, heart failure and lactic acidosis: is Metformin absolutely contraindicated?. BMJ. 2007, 355: 508-512. sourceExperimental — accuracy not yet measured
Table 1 (Conclusions) says pharmacological differences between metformin and phenformin might explain metformin’s lower incidence of lactic acidosis. It supports poor mitochondrial-membrane adherence, no interference with lactate turnover, and unchanged excretion for metformin. However, the citing sentence appears to attribute inhibition of electron transport and glucose oxidation to metformin; the table marks both as absent for metformin and present for phenformin. (LLM, conf=0.88)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Even after including the wash out period in the overall analysis, metformin still significantly decreased diabetes incidence (risk ratio 0.75, p = 0.005) compared with placebo [8].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [8] Diabetes Prevention Program Research Group: Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. Diabetes Care. 2003, 26 (4): 977-980. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The association of IFG with cardiovascular events, however, has not been well established [6].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [6] Petersen J, Mc Guire D: Impaired glucose tolerance and impaired fasting glucose – a review of diagnosis, clinical implications and management. Diabetes Vasc Dis Res. 2005, 2 (1): 9-15. 10.3132/dvdr.2005.007. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) statuses are associated with increased and varying risk of developing type 2 diabetes mellitus.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [6] Petersen J, Mc Guire D: Impaired glucose tolerance and impaired fasting glucose – a review of diagnosis, clinical implications and management. Diabetes Vasc Dis Res. 2005, 2 (1): 9-15. 10.3132/dvdr.2005.007. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that, at least in the short-term, metformin may help delay the onset of diabetes.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The relative risk reduction was 28.5% with lifestyle modification (p = 0.018), 26.4% with metformin (p = 0.029), and 28.2% with lifestyle modification plus metformin (p = 0.022), as compared with the control group [9] (Table 1).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [9] Ramachandran A, Snehalatha C, Mukesh M: Indian diabetes prevention programme (IDPP). the Indian diabetes prevention programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006, 49: 289-297. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Inhibition of mitochondrial respiration has also been proposed to contribute to the reduction of gluconeogenesis since it reduces the energy supply required for this process [3].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction
What the sources say
- Not checked yetcites [3] El-Mir MY, Nogueira V, Fontaine E: Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000, 275: 223-228. 10.1074/jbc.275.1.223. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Acarbose reduces the bioavailability of metformin [37].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and α glicosidase inhibitor
What the sources say
- Not checked yetcites [37] Scheen AJ, de Magalhanes AC, Salvatore T: Reduction of the acute bioavailability of metformin by the α glycosidase inhibitor acarbose in normal man. Eur J Clin Invest. 1994, 24 (Suppl3): 50-54. source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The prevalence of pre-diabetes as well as the progression rate to diabetes may differ between different populations, making the application of results from certain studies of different ethnical groups inappropriate.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The addition of metformin to insulin therapy in type 1 diabetes is also associated with reductions in insulin-dose requirement and HbA1c levels [30,31].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and insulin
What the sources say
- Not checked yetcites [30] Vella S, Buetow L, Royle P: The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010, 53 (5): 809-820. 10.1007/s00125-009-1636-9. source
- Not checked yetcites [31] Abdelghaffar S, Attia AM: Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents. Cochrane Database Syst Rev. 2009, CD006691-Issue 1 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Lily and Godwin reported a decreased rate of conversion from pre-diabetes to diabetes in individuals with IGT or IFG in their systematic review and meta-analysis of randomized controlled trials.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [15] Lily M, Godwin M: Treating prediabetes with metformin systematic review and meta-analysis. Can Fam Physician. 2009, 55: 363-369.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin and sulfonylurea combination therapy was also associated with reduced all-cause mortality [26].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and sulfonylureas
What the sources say
- Not checked yetcites [26] Johnson JA, Majumdar SR, Simpson SH: Decreased mortality associated with the use of metformin compared with sulfonylurea Monotherapy in type 2 diabetes. Diabetes Care. 2002, 25: 2244-2248. 10.2337/diacare.25.12.2244. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Diabetes incidence 10 years since DPP randomization was reduced by 34% and 18% in the lifestyle and metformin group, respectively [11] (Table 1).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [11] Diabetes Prevention Program Research Group: 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009, 374 (9702): 1677-1686. 10.1016/S0140-6736(09)61457-4. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Patients who started SUs first and added metformin also had higher rates of cardiovascular disease events compared with those who started metformin first and added SUs.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and sulfonylureas
What the sources say
- Not checked yetcites [27] Evans JM, Ogston SA, Emslie-Smith A, Morris AD: Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia. 2006, 49: 930-936. 10.1007/s00125-006-0176-9. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin has been also been shown to be effective in normal weight patients [19].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in the management of adult diabetic patients
What the sources say
- Not checked yetcites [19] Ito H, Ishida H, Takeuchi Y: Long-term effect of metformin on blood glucose control in non-obese patients with type 2 diabetes mellitus. Nutr Metab. 2010, 7: 83-10.1186/1743-7075-7-83. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In a meta-analysis of randomized controlled trials, Salpeter et al. reported a reduction of 40% in the incidence of new-onset diabetes with an absolute risk reduction of 6% (95% CI, 4–8) during a mean trial duration of 1.8 years [14].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [14] Salpeter SR, Buckley NS, Kahn JA: Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med. 2008, 121: 149-157. 10.1016/j.amjmed.2007.09.016. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The combination of metformin and sulfonylurea (SU) is one of the most commonly used and can attain a greater reduction in HbA1c (0.8–1.5%) than either drug alone [23,24].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and sulfonylureas
What the sources say
- Not checked yetcites [23] Charbonnel B, Shernthaner G, Brunetti P: Long-term efficacy and tolerability of add-on piogçitazone therapy to faliling monotherapy compared with addition of glicazide or metformin in patients with type 2 diabetes. Diabetologia. 2005, 48: 1093-1104. 10.1007/s00125-005-1751-1. source
- Not checked yetcites [24] Hanefeld M, Brunetti P, Schhernthaner GH: One year glycemic control with sulphonylurea plus pioglitazone versus sulphonylurea plus metformin in patients with type 2 diabetes. Diabetes Care. 2004, 27: 141-147. 10.2337/diacare.27.1.141. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Epidemiological investigations suggest that patients on SUs have a higher cardiovascular disease event rate than those on metformin.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and sulfonylureas
What the sources say
- Not checked yetcites [27] Evans JM, Ogston SA, Emslie-Smith A, Morris AD: Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia. 2006, 49: 930-936. 10.1007/s00125-006-0176-9. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Combinations of metformin and insulin secretagogue can reduce HbA1c between 1.5% to 2.2% in patients sub-optimally controlled by diet and exercise [21].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in combination therapy
What the sources say
- Not checked yetcites [21] Gerich J, Raskin P, Jean-Louis L: PRESERVE-beta: two-year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin. Diabetes Care. 2005, 28: 2093-2099. 10.2337/diacare.28.9.2093. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Sulfonylureas and glinides were associated with higher rates of hypoglycemia than with placebo.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in combination therapy
What the sources say
- Not checked yetcites [22] Phung OJ, Scholle JM, Talwar M, Coleman CI: Effect of noninsulin Antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010, 303 (14): 1410-1418. 10.1001/jama.2010.405. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Dapagliflozin, a highly selective inhibitor of SGLT2, has demonstrated efficacy, alone or in combination with metformin, in reducing hyperglycemia in patients with type 2 diabetes [35,36].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and glifozins
What the sources say
- Not checked yetcites [35] Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M: Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther. 2009, 85: 513-519. 10.1038/clpt.2008.250. source
- Not checked yetcites [36] List JF, Woo V, Morales E, Tang W, Fiedorek FT: Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009, 32: 650-657. 10.2337/dc08-1863. source
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In the paper
“The UKPDS demonstrated that metformin is as effective as sulfonylurea in controlling blood glucose levels of obese patients with type 2 diabetes mellitus [18].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in the management of adult diabetic patients
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
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In the paper
“Results of the MiG TOFU reported that infants of diabetic mothers exposed to metformin in utero and examined at 2 years of age may present a reduction in insulin resistance, probably related to an increase in subcutaneous fat [48].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pregnancy
What the sources say
- Not checked yetcites [48] Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM: Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Diabetes Care. 2011, 34: 2279-2284. 10.2337/dc11-0660. source
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In the paper
“However, it has been reported that the association of acarbose to metformin in sub-optimally controlled patients reduced HbA1c by about 0.8-1.0% [38].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and α glicosidase inhibitor
What the sources say
- Not checked yetcites [38] Rosenstok J, Brown A, Fischer J: Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes. Diabetes Care. 1998, 21: 2050-2055. 10.2337/diacare.21.12.2050. source
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In the paper
“A reduction in ALT, GGT, and fatty liver incidence and severity has also been described with metformin use [60].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin indications for management of obesity, insulin resistance, and non-alcoholic fatty liver in children and adolescents
What the sources say
- Not checked yetcites [60] Tock L, Dˆamaso A, de Piano A, Carnier J: Long-TermEffects of metformin and lifestyle modification on nonalcoholic fatty liver disease obese adolescents. J Obes. 2010, 831901: 6-Article ID 831901
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In the paper
“Metformin is known to cross the placenta and concerns regarding potential adverse effects on both the mother and the fetus have limited its use in pregnancy [43].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pregnancy
What the sources say
- Not checked yetcites [43] Charles B, Norris R, Xiao X, Hague W: Population pharmacokinetics of metformin in late pregnancy. Ther Drug Monit. 2006, 28: 67-72. 10.1097/01.ftd.0000184161.52573.0e. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Two meta-analyses of observational studies, one of women using metformin and/or sulfonylureas and one of women using metformin alone during the first trimester, did not show an increase in congenital malformations or neonatal deaths [44,45].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pregnancy
What the sources say
- Not checked yetcites [44] Gutzin SJ, Kozer E, Magee LA, Feig DS, Koren G: The safety of oral hypoglycemic agents in the first trimester of pregnancy. a meta-analysis. Can J Clin Pharmacol. 2003, 10: 179-183.
- Not checked yetcites [45] Gilbert C, Valois M, Koren G: Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril. 2006, 86: 658-663. 10.1016/j.fertnstert.2006.02.098. source
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In the paper
“Metformin provided greater protection against the development of macrovascular complications than would be expected from its effects upon glycemic control alone.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The beneficial role of metformin in young patients with type 2 diabetes has been demonstrated in a randomized, controlled trial which showed a significant decrease in fasting blood glucose, HbA1c, weight, and total cholesterol.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin use in childhood and adolescence
What the sources say
- Not checked yetcites [51] Jones KL, Arslanian S, Peterokova VA, Park JS, Tomlinson MJ: Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2002, 25: 89-94. 10.2337/diacare.25.1.89. source
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In the paper
“The HOME trial reported a decreased risk of developing macrovascular disease [75].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [75] Kooy A, de Jager J, Lehert P: Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. 2009, 169: 616-625. 10.1001/archinternmed.2009.20. source
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In the paper
“In 1980, Scambato et al. reported that, in a 3-year observational study of 310 patients with ischaemic cardiomyopathy, patients treated with metformin had reduced rates of re-infarction, occurrence of angina pectoris, acute coronary events other than acute myocardial infarction, and death in patients [72].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [72] Sgambato S, Varricchio M, Tesauro P, Passariello N, Carbone L: Use of metformin in ischemic cardiopathy. Clin Ther. 1980, 94: 77-85.
plaindirectn = 310 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“Long-acting GLP-1 receptor agonists reduced HbA1c and fasting glucose levels to a greater extent than the other therapies [42].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and incretin-based therapies
What the sources say
- Not checked yetcites [42] Deacon CF, Mannucci E, Ahrén B: Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2 diabetes-a review and meta analysis. Diabetes Obes Metab. 2012, 14 (8): 762-767. 10.1111/j.1463-1326.2012.01603.x. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“There is some evidence that suggests improvement in metabolic control of poorly controlled adolescents with type 1 diabetes when metformin is added to insulin therapy.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin use in childhood and adolescence
What the sources say
- Not checked yetcites [30] Vella S, Buetow L, Royle P: The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010, 53 (5): 809-820. 10.1007/s00125-009-1636-9. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In non-diabetic subjects with normal coronary arteriography but also with two consecutive positive (ST depression > 1 mm) exercise tolerance test, an 8-week period on metformin improved maximal ST-segment depression, Duke score, and chest pain incidence compared with placebo [76].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [76] Jadhav S, Ferrell W, Greer IA, Petrie JR, Cobbe SM, Sattar N: Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries. J Am Coll Cardiol. 2006, 48: 956-963. 10.1016/j.jacc.2006.04.088. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Saxagliptin added to metformin led to clinically and statistically significant reductions in HbA1c from baseline versus metformin/placebo in a 24-week randomized, double-blind, placebo-controlled trial.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and incretin-based therapies
What the sources say
- Not checked yetcites [41] DeFronzo RA, Hissa MN, Garber AJ, for Saxagliptin Study Group: The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009, 32 (9): 1649-1655. 10.2337/dc08-1984. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These effects are probably direct and not related to decreases in hyperglycemia [88].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on endothelial function
What the sources say
- Not checked yetcites [88] De Jager J, Kooy A, Lehert P: Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2004, 256: 1-14. 10.1111/j.1365-2796.2004.01328.x. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“There were no differences between groups in all-cause mortality, cardiovascular mortality, rate of myocardial infarction, or rate of cardiovascular events [84].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [84] Rachmani R, Slavachevski I, Levi Z, Zadok B, Kedar Y, Ravid M: Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med. 2002, 13: 428-433. 10.1016/S0953-6205(02)00131-0. source
plainn = 393- Asserted: passes — The authors put it forward as true.
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In the paper
“The improved cardiovascular disease (CVD) risk in overweight diabetic patients treated with metformin was attributed to its effects extending beyond glycemic control [18].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Beyond glycemic control
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Many different mechanisms, beyond glycemic control, have been implicated in vascular protection induced by metformin such as improvements in the inflammatory pathway [86], coagulation [87], oxidative stress and glycation [88-92], endothelial dysfunction [88-90], haemostasis [88,91-93], insulin resistance improvement [94], lipid profiles [95,96], and fat redistribution [97,98].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [86] Isoda K, Young J, Zirlik A: Metformin inhibits Proinflammatory Responses and Nuclear Factor ĸß in Human Vascular Wall Cells. Arterioscler Thromb Vasc Biol. 2006, 26: 611-617. source
- Not checked yetcites [87] The Diabetes Prevention Program Research Group Intensive: Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance. Diabetes. 2005, 54 (5): 1566-1572. source
- Not checked yetcites [88] De Jager J, Kooy A, Lehert P: Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2004, 256: 1-14. 10.1111/j.1365-2796.2004.01328.x. source
- Not checked yetcites [89] Mather KJ, Verma S, Anderson TJ: Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001, 37 (5): 1344-1350. 10.1016/S0735-1097(01)01129-9. source
- Not checked yetcites [90] Vitale C, Mercuro G, Cornoldi A, Fini M: Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med. 2005, 258: 250-256. 10.1111/j.1365-2796.2005.01531.x. source
- Not checked yetcites [91] Grant PJ: Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003, 29 (6S): 44-52.
- Not checked yetcites [92] Standeven KF, Ariens RA, Whitaker P: The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Diabetes. 2002, 51: 189-197. source
- Not checked yetcites [93] Charles MA, Morange P, Eschwege E: Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity. Diabetes Care. 1998, 21: 1967-1972. 10.2337/diacare.21.11.1967. source
- Not checked yetcites [94] Wu RR, Zhao JP, Jin H: Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain A Randomized Controlled Trial. JAMA. 2008, 299 (2): 185-193. 10.1001/jama.2007.56-b. source
- Not checked yetcites [95] Glueck CJ, Fontaine RN, Wang P: Metformin reduces weight, centripetalobesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001, 50: 856-861. 10.1053/meta.2001.24192. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Despite all its benefits, metformin is contraindicated in patients with heart failure due to the potential risk of developing lactic acidosis, a rare but potentially fatal metabolic condition resulting from severe tissue hypoperfusion [79].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [79] Hulisz DT, Bonfiglio MF, Murray RD: Metformin-associated lactic acidosis. J Am Board Fam Pract. 1998, 11: 233-236. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin may have a neutral effect on body weight of patients with T2DM when compared to diet [18]”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin can act as an inhibitor of pro-inflammatory responses through direct inhibition of NF-kB by blocking the PI3K–Akt pathway.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on the inflammatory pathway
What the sources say
- Not checked yetcites [86] Isoda K, Young J, Zirlik A: Metformin inhibits Proinflammatory Responses and Nuclear Factor ĸß in Human Vascular Wall Cells. Arterioscler Thromb Vasc Biol. 2006, 26: 611-617. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“or may limit or decrease the weight gain experienced with sulfonylureas [18], TDZ [104], insulin [29,75], HAART [97], and antipsychotics drugs [94].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
- Not checked yetcites [104] Kahn SE, Haffner SM, Heise MA: Glycemic durability of rosiglitazone, metformin or glyburide monotherapy. N Engl J Med. 2006, 355: 2427-2443. 10.1056/NEJMoa066224. source
- Not checked yetcites [29] Lund SS, Tarnow L, Frandsen M: Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. BJ. 2009, 339: b4324-10.1136/bmj.b4324. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“After a multivariate adjustment for demographics, cardiac function, renal function, and HF medications, metformin therapy was associated with a non-significant trend of improved survival [85].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [85] Shah DD, Fonarow GC, Horwich TB: Metformin Therapy and Outcomes in Patients With Advanced Systolic Heart Failure and Diabetes. J Card Fail. 2010, 16 (3): 200-206. 10.1016/j.cardfail.2009.10.022. source
hedgedcorrelationaln = 401- Asserted: passes — The authors put it forward as true.
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In the paper
“Type 2 diabetes is associated with a progressive and generalized impairment of endothelial function that affects the regulation of vasomotor tone, leucocyte adhesion, hemostasis, and fibrinolysis.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on endothelial function
What the sources say
- Not checked yetcites [88] De Jager J, Kooy A, Lehert P: Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2004, 256: 1-14. 10.1111/j.1365-2796.2004.01328.x. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“One-year survival in metformin-treated and non-metformin-treated patients was 91% and 76%, respectively (p = 0.007).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [85] Shah DD, Fonarow GC, Horwich TB: Metformin Therapy and Outcomes in Patients With Advanced Systolic Heart Failure and Diabetes. J Card Fail. 2010, 16 (3): 200-206. 10.1016/j.cardfail.2009.10.022. source
plaincorrelationaln = 401 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“AMPK is activated in the brain by metabolic stresses that inhibit ATP production such as ischemia, hypoxia, glucose deprivation, metabolic inhibitors (metformin), as well as catabolic and ATP consuming processes [122].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [122] Santomauro Júnior AC, Ugolini MR, Santomauro AT, Souto RP: Metformina e AMPK: Um Antigo Fármaco e Uma Nova Enzima no Contexto da Síndrome Metabólica. Arq Bras Endocrinol Metabol. 2008, 52 (1): 120-125. 10.1590/S0004-27302008000100017. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, plasma levels of PAI-1 and vWF, which are secreted mainly by the impaired endothelium, have been shown to decrease with metformin therapy in non-diabetic subjects [93].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on hemostasis
What the sources say
- Not checked yetcites [93] Charles MA, Morange P, Eschwege E: Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity. Diabetes Care. 1998, 21: 1967-1972. 10.2337/diacare.21.11.1967. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Metformin has been shown to reduce VAT [97,98]”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [97] Hadigan C, Corcoran C, Basgoz N: Metformin in the Treatment of HIV Lipodystrophy Syndrome A Randomized Controlled Trial. JAMA. 2000, 284: 472-477. 10.1001/jama.284.4.472. source
- Not checked yetcites [98] Sheth S, Larson L: The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. BMC Infect Dis. 2010, 10: 183-10.1186/1471-2334-10-183. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“while protease inhibitors (PIs) have been associated with biochemical derangements of glucose and lipids as well as with localized accumulation of fat [117].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [117] Behrens G, Dejam A, Schmidt H: Impaired glucose tolerance, b cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. Acquir Immune Defic Syndr. 1999, 13: F63-F70.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Modest weight loss with metformin has been observed in subjects with IGT [15,18].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [15] Lily M, Godwin M: Treating prediabetes with metformin systematic review and meta-analysis. Can Fam Physician. 2009, 55: 363-369.
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
plainconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“and may contribute to hypertension by increasing sympathetic activity, peripheral vascular resistance, renal sodium retention [107], and vascular smooth muscle tone and proliferation [108,109].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on blood pressure
What the sources say
- Not checked yetcites [107] Wulffelé MG, Kooy A, Lehert P, Bets D, Donker A, Stehouwer C: Does metformin decrease blood pressure in patients with type 2 diabetes intensively treated with insulin?. Diabet Med. 2005, 22: 907-10.1111/j.1464-5491.2005.01554.x. source
- Not checked yetcites [108] Tack CJ, Smits P, Willemsen JJ, Lenders JW, Thien T, Lutterman JA: Effects of insulin on vascular tone and sympathetic nervous system in NIDDM. Diabetes. 1996, 45: 15-22. 10.2337/diabetes.45.1.15. source
- Not checked yetcites [109] Sechi LA, Bartoli E: Molecular mechanisms of insulin resistance in arterial hypertension. Blood Press Suppl. 1996, 1: 47-54.
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In the paper
“reduction of leptin [95] and ghrelin levels after glucose overload [96]”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [95] Glueck CJ, Fontaine RN, Wang P: Metformin reduces weight, centripetalobesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001, 50: 856-861. 10.1053/meta.2001.24192. source
- Not checked yetcites [96] Kusaka I, Nagasaka S, Horie H, Ishibashi S: Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability?. Diabetes Obes Metab. 2008, 10: 1039-1046. 10.1111/j.1463-1326.2008.00857.x. source
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In the paper
“but at the expense of accelerating peripheral fat loss [118].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [118] Kohli R, Shevitz A, Gorbach S, Wanke C: A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy. HIV Med. 2007, 8: 420-426. 10.1111/j.1468-1293.2007.00488.x. source
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In the paper
“Data of the effects of metformin on BP are variable, with neutral effects or small decreases in SBP and DBP [110].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on blood pressure
What the sources say
- Not checked yetcites [110] Granberry MC, Fonseca VA: Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. Am J Cardiovasc Drugs. 2005, 5: 201-209. 10.2165/00129784-200505030-00006. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance is related to hypertension in both diabetic and non-diabetic individuals”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on blood pressure
What the sources say
- Not checked yetcites [107] Wulffelé MG, Kooy A, Lehert P, Bets D, Donker A, Stehouwer C: Does metformin decrease blood pressure in patients with type 2 diabetes intensively treated with insulin?. Diabet Med. 2005, 22: 907-10.1111/j.1464-5491.2005.01554.x. source
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In the paper
“In this setting, the permeability transition pore (PTP) acts as a regulator of the apoptotic cascade under stress conditions, triggering the release of apoptotic proteins and subsequent cell death [127].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [127] Plum L, Schubert M, Bruning JC: The role of insulin receptor signaling in the brain. Trends Endocrinol Metab. 2005, 16: 59-65. 10.1016/j.tem.2005.01.008. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and by induction of a lipolitic and anoretic effect by acting on glucagon–like peptide 1 [40].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [40] Mannucci E, Ognibene A, Cremasco F: Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care. 2001, 24: 489-494. 10.2337/diacare.24.3.489. source
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In the paper
“In the BIGPRO1 trial carried out in upper-body obese non-diabetic subjects with no cardiovascular diseases or contraindications to metformin, blood pressure decreased significantly more in the IFG/IGT subgroup treated with metformin compared to the placebo group (p < 0.03) [111].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on blood pressure
What the sources say
- Not checked yetcites [111] Fontbonne A, Diouf I, Baccara-Dinet M, Eschwege E, Charles A: Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: a post-hoc analysis of the BIGPRO1 trial. Diabetes Metab. 2009, 35: 385-391. 10.1016/j.diabet.2009.03.005. source
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In the paper
“Antiretroviral therapy has been associated with an increased prevalence of type 2 diabetes mellitus and insulin resistance among HIV-infected patients [114].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [114] Triant VA, Lee H, Hadigan C, Grinspoon SK: Increased acute myocardial infarction rates and cardiovascular risk factors among patients with HIV disease. J Clin Endocrinol Metab. 2007, 92: 2506-2512. 10.1210/jc.2006-2190. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“It is a brain specific form of diabetes characterized by impaired insulin actions and neuronal insulin resistance [120] that leads to excessive generation and accumulation of amyloid oligomers, a key factor in the development of AD [121].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [120] Spasic MR, Callaerts P, Norga KK: AMP-Activated Protein Kinase (AMPK) Molecular Crossroad for Metabolic Control and Survival of Neurons. Neuroscientist. 2009, 15 (4): 309-316. 10.1177/1073858408327805. source
- Not checked yetcites [121] Culmsee C, Monnig J, Kemp BE, Mattson MP: AMPactivated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci. 2001, 17: 45-58. 10.1385/JMN:17:1:45. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin decreases serum levels of thyrotropin (TSH) to subnormal levels in hypothyroid patients that use levothyroxin (LT4) on a regular basis [112].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on thyroid function
What the sources say
- Not checked yetcites [112] Vigersky R, Filmore-Nassar A, Allan R: Thyrotropin Suppression by Metformin. J Clin Endocrinol Metab. 2006, 91: 225-227. 10.1210/jc.2005-1210. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, a meta-analysis of overweight and obese non-diabetic subjects, found no significant weight loss as either a primary or as secondary outcome [105].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [105] Desilets AR, Dhakal-Karki S, Dunican KC: Role of metformin for weight management in patients without type 2 diabetes. Ann Pharmacother. 2008, 42: 817-826. 10.1345/aph.1K656. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The mechanisms by which metformin contributes to weight loss may be explained through the reduction in gastrointestinal absorption of carbohydrates and insulin resistance [95]”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on body weight
What the sources say
- Not checked yetcites [95] Glueck CJ, Fontaine RN, Wang P: Metformin reduces weight, centripetalobesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001, 50: 856-861. 10.1053/meta.2001.24192. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The human brain is characterized by an elevated oxidative metabolism and low antioxidants enzymes, which increases the brain’s vulnerability to oxidative stress [125].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [125] Kroemer G, Reed JC: Mitochondrial control of cell death. Nat Med. 2000, 6: 513-519. 10.1038/74994. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Therapeutic doses of metformin in type 2 diabetic patients lower circulating levels of several coagulation factors such as plasminogen activator inhibitor (PAI-1), von Williebrand Factor (vWF), tissue type plasminogen activator [88], factor VII [91].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on hemostasis
What the sources say
- Not checked yetcites [88] De Jager J, Kooy A, Lehert P: Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2004, 256: 1-14. 10.1111/j.1365-2796.2004.01328.x. source
- Not checked yetcites [91] Grant PJ: Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003, 29 (6S): 44-52.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [147] Bowker SL, Majumdar SR, Veugelers P, Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who usesulfonylureas or insulin. Diabetes Care. 2006, 29: 254-258. 10.2337/diacare.29.02.06.dc05-1558. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Patients with type 2 diabetes have increased risks of various types of cancer, particularly liver, pancreas, endometrium, colon, rectum, breast, and bladder cancer.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [133] Papanas N, Maltezos E, Mikhailidis DP: Metformin and cancer: licence to heal?. Expert Opin Investig Drugs. 2010, 19: 913-917. 10.1517/13543784.2010.499122. source
- Not checked yetcites [134] Larsson SC, Orsini N, Wolk A: Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Canc Ins. 2005, 97: 1679-1687. 10.1093/jnci/dji375. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Cancer mortality is also increased [133,134].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [133] Papanas N, Maltezos E, Mikhailidis DP: Metformin and cancer: licence to heal?. Expert Opin Investig Drugs. 2010, 19: 913-917. 10.1517/13543784.2010.499122. source
- Not checked yetcites [134] Larsson SC, Orsini N, Wolk A: Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Canc Ins. 2005, 97: 1679-1687. 10.1093/jnci/dji375. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin may have additional anticancer properties independent of AMPK, liver kinase 1 (LKB1), and TSC2. This may be related, in part, to the inhibition of Rag GTPase-mediated activation of mTOR [145].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [145] Evans J, Donelly L, Emslie A: Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005, 330 (7503): 1304-1305. 10.1136/bmj.38415.708634.F7. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“An observational cohort study with type 2 diabetics who were new metformin users found a significant decrease in cancer incidence among metformin users (7.3%) compared to controls (11.6%). The unadjusted hazard ratio (95% CI) for cancer was 0.46 (0.40–0.53).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [136] Donadon V, Balbi M, Valent F, Avogaro A: Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenterol. 2010, 16 (24): 3025-3032. 10.3748/wjg.v16.i24.3025. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Activation of AMPK leads to inhibition of mTOR through phosphorylaton and subsequent activation of the tumor suppressor tuberous sclerosis complex 2 (TSC2).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [144] Kalender A, Selvaraj A, Kim SY: Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPasedependent manner. Cell Metab. 2010, 11: 390-401. 10.1016/j.cmet.2010.03.014. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It was reported that metformin prevents PTP opening and subsequent cell death in various endothelial cell types exposed to high glucose levels [128].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [128] van der Heide LP, Ramakers GM, Smidt MP: Insulin signaling in the central nervous system: learning to survive. Prog Neurobiol. 2006, 79: 205-221. 10.1016/j.pneurobio.2006.06.003. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In an observational study of women with type 2 diabetes, a decreased risk of breast cancer among metformin users was only seen with long-term use [137].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [137] Libby G, Donnelly LA, Donnan PT: New users of metformin area at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009, 32: 1620-1625. 10.2337/dc08-2175. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Patients with type 2 diabetes who are prescribed metformin had a lower risk of cancer compared to patients who did not take it.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [135] Li D, Yeung SJ, Hassan MM, Konopleva M, Abbruzzese JL: Anti-diabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009, 137 (2): 482-488. 10.1053/j.gastro.2009.04.013. source
- Not checked yetcites [136] Donadon V, Balbi M, Valent F, Avogaro A: Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenterol. 2010, 16 (24): 3025-3032. 10.3748/wjg.v16.i24.3025. source
- Not checked yetcites [137] Libby G, Donnelly LA, Donnan PT: New users of metformin area at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009, 32: 1620-1625. 10.2337/dc08-2175. source
- Not checked yetcites [138] Landman GW, Kleefstra N, van Hateren KJ: Metformin associated with lower cancer mortality in type 2 diabetes ZODIAC-16. Diabetes Care. 2010, 33: 322-326. 10.2337/dc09-1380. source
- Not checked yetcites [139] Lee JH, Kim TI, Jeon SM: The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer. 2011, 12: 1-24. source
- Not checked yetcites [145] Evans J, Donelly L, Emslie A: Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005, 330 (7503): 1304-1305. 10.1136/bmj.38415.708634.F7. source
- Not checked yetcites [146] Bodmer M, Meier C, Krähenbühl S: Long-term metformin Use is associated with decreased risk of breast cancer. Diabetes Care. 2010, 33: 1304-1308. 10.2337/dc09-1791. source
- Not checked yetcites [147] Bowker SL, Majumdar SR, Veugelers P, Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who usesulfonylureas or insulin. Diabetes Care. 2006, 29: 254-258. 10.2337/diacare.29.02.06.dc05-1558. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin could interrupt the apoptotic cascade in a model of ectoposide-induced cell death by inhibiting PTP opening and blocking the release of cytochrome-c.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [125] Kroemer G, Reed JC: Mitochondrial control of cell death. Nat Med. 2000, 6: 513-519. 10.1038/74994. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Diabetic patients with colorectal cancer who were treated with metformin had lower mortality than those not receiving metformin [139].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [139] Lee JH, Kim TI, Jeon SM: The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer. 2011, 12: 1-24. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Metformin use is associated with lower cancer-related mortality.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [138] Landman GW, Kleefstra N, van Hateren KJ: Metformin associated with lower cancer mortality in type 2 diabetes ZODIAC-16. Diabetes Care. 2010, 33: 322-326. 10.2337/dc09-1380. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“With regard to ß amyloid, a report has shown that metformin increases ß amyloid in cells through an AMPK-dependent mechanism, independent of insulin signaling and glucose metabolism. This effect is mediated by a transcriptional upregulation of ß secretase (BACE 1) which leads to an increase of ß amyloid [131].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [131] Chen Y, Zhoua K, Wanga R, Liua Y: Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via up-regulating BACE1 transcription. PNAS. 2009, 106 (10): 3907-3912. 10.1073/pnas.0807991106. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A multicentric study reported a mean decrease of 19% and 5% in vitamin B12 and folate concentration, respectively [168].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [168] Jager J, Kooy A, Lehert P, Wulffelé M: Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomized placebo controlled trial. BMJ. 2010, 340: c2181-10.1136/bmj.c2181. source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In vitro and in vivo studies strongly suggest that metformin may be a valuable adjuvant in cancer treatment.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“This may reduce tumor mass and prevent relapse more effectively than either drug used as monotherapy [157].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
What the sources say
- Not checked yetcites [157] Hirsh H, Iliopoulos D, Tsichlis P, Stuh K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009, 69 (19): 7507-7511. 10.1158/0008-5472.CAN-09-2994. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Most are mainly mediated through AMPK activation which requires LKB1, a well-known tumor suppressor [2].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [2] Shaw RJ, Lamia KA, Vasquez D: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005, 310: 1642-1646. 10.1126/science.1120781. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Despite the use of metformin in cases where it is contraindicated, the incidence of lactic acidosis has not increased.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin contraindications
What the sources say
- Not checked yetcites [161] Tahrani AA, Varghese GI, Scarpello JH, Hanna FWF: Metformin, heart failure and lactic acidosis: is Metformin absolutely contraindicated?. BMJ. 2007, 355: 508-512. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Another clinical condition associated with lactic acidosis in patients using metformin is heart failure [79].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin contraindications
What the sources say
- Not checked yetcites [79] Hulisz DT, Bonfiglio MF, Murray RD: Metformin-associated lactic acidosis. J Am Board Fam Pract. 1998, 11: 233-236. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Most patients with case reports relating metformin to lactic acidosis had at least one or more predisposing conditions for lactic acidosis [161].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin contraindications
What the sources say
- Not checked yetcites [161] Tahrani AA, Varghese GI, Scarpello JH, Hanna FWF: Metformin, heart failure and lactic acidosis: is Metformin absolutely contraindicated?. BMJ. 2007, 355: 508-512. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The association of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
What the sources say
- Not checked yetcites [157] Hirsh H, Iliopoulos D, Tsichlis P, Stuh K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009, 69 (19): 7507-7511. 10.1158/0008-5472.CAN-09-2994. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Gastrointestinal intolerance occurs quite frequently in the form of abdominal pain, flatulence, and diarrhea [164].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [164] Metformin LS: Metformin: a review of its pharmacological properties and therapeutic use. Diabetes Metab. 1979, 5: 233-245.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Low doses of metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer in a mouse xenograft model.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
What the sources say
- Not checked yetcites [157] Hirsh H, Iliopoulos D, Tsichlis P, Stuh K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009, 69 (19): 7507-7511. 10.1158/0008-5472.CAN-09-2994. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Most of these effects are transient and subside once the dose is reduced or when administered with meals.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [164] Metformin LS: Metformin: a review of its pharmacological properties and therapeutic use. Diabetes Metab. 1979, 5: 233-245.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Type 2 diabetic patients receiving neo-adjuvant chemotherapy for breast cancer as well as metformin were more likely to have pathologic complete response (pCR) than patients not receiving it.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
What the sources say
- Not checked yetcites [156] Jiralerspong S, Palla S, Giordano S: Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer. J Clin Oncol. 2009, 27: 3297-3302. 10.1200/JCO.2009.19.6410. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, despite the increase in pCR, metformin did not significantly improve the estimated 3-year relapse-free survival rate [156].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
What the sources say
- Not checked yetcites [156] Jiralerspong S, Palla S, Giordano S: Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer. J Clin Oncol. 2009, 27: 3297-3302. 10.1200/JCO.2009.19.6410. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Clinically significant drug interactions involving metformin are rare.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Drug interactions
What the sources say
- Not checked yetcites [175] Glucophage® and Glucophage XRproduct information. Bristol-Myers Squibb Company. 2003, Available at: http://www.drugs.com/pro/glucophage.html
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Other studies have found good to excellent glycemic control with metformin XR in type 2 diabetic patients who did not have well-controlled diet and exercise alone [182].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin XR
What the sources say
- Not checked yetcites [182] Raz I, Delaet I, Goyvaerts H: Safety and efficacy of novel extended-release formulation of metformin in patients with type 2 diabetes. Diabetes. 2000, 49 (Suppl 1): A363-
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 66
- Probably not a substantial claim. 21
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“It can upregulate uncoupled proteins 2 (UCP2) in adipose tissue [102] and can also cause an increase in reduced glutathione [100].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on oxidative stress
What the sources say
- Supportedcites [102] Anedda A, Rial E, Gonzalez Barroso : Metformin induces oxidative stress in white adipocytes and raises uncoupling proten levels. J Endocrinol. 2008, 199: 33-40. 10.1677/JOE-08-0278. source
The Results section, “Metformin induces the expression of UCP2 in mouse white adipose tissue” (page not provided), reports that UCP2 protein increased markedly in mouse white adipose tissue after metformin treatment. Citation [102] is attached only to the UCP2 claim; the reduced-glutathione claim is attributed to [100] and is not part of this verdict. (LLM, conf=0.94)
- Not checked yetcites [100] Faure P, Rossini E, Wiernsperger N: An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Diabetes. 1999, 48: 353-357. 10.2337/diabetes.48.2.353. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
In the paper
“Diabetes incidence increased from 25.2 to 30.6% in the metformin group and from 33.4 to 36.7% in the placebo group.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [8] Diabetes Prevention Program Research Group: Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. Diabetes Care. 2003, 26 (4): 977-980. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“IGT has been associated with an increased risk of cardiovascular events and may determine an increased mortality risk.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [6] Petersen J, Mc Guire D: Impaired glucose tolerance and impaired fasting glucose – a review of diagnosis, clinical implications and management. Diabetes Vasc Dis Res. 2005, 2 (1): 9-15. 10.3132/dvdr.2005.007. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Metformin’s efficacy, security profile, benefic cardiovascular and metabolic effects, and its capacity to be associated with other antidiabetic agents makes this drug the first glucose lowering agent of choice when treating patients with type 2 diabetes mellitus (TDM2).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: Aggressive treatment is required in type 2 diabetes mellitus to achieve glycemic and cardiovascular risk factor goals.
In the paper
“Treatment with metformin or acarbose produced large, significant, and similar risk reductions for new onset of T2DM of 77% and 88%, respectively; these reductions were larger than that of lifestyle intervention alone [10].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [10] Yang W, Lin L, Qi J: The preventive effect of acarbose and metformin on the IGT population from becoming diabetes mellitus: a 3-year multicentral prospective study. Chin J Endocrinol Metab. 2001, 17: 131-134.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In their systematic review, Gillies et al. found that lifestyle and pharmacological interventions reduced the rate of progression to type 2 diabetes in people with IGT and that these interventions seem to be as effective as pharmacological treatment.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [5] Guillies C, Abram KR, Lambert PC, Cooper NJ, Sutton AJ: Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007, 334: 299-10.1136/bmj.39063.689375.55. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lifestyle intervention and metformin reduced diabetes incidence by 58% and 31%, respectively, when compared with placebo [7].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [7] Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002, 346: 393-403. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These effects are mediated by the activation of an upstream kinase, liver kinase B1 (LKB-1), which in turn regulates the downstream kinase adenosine monophosphatase protein kinase (AMPK). AMPK phosphorylates a transcriptional co-activator, transducer of regulated CREB protein 2 (TORC2), resulting in its inactivation which consequently downregulates transcriptional events that promote synthesis of”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction
What the sources say
- Not checked yetcites [2] Shaw RJ, Lamia KA, Vasquez D: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005, 310: 1642-1646. 10.1126/science.1120781. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin acts primarily at the liver by reducing glucose output and, secondarily, by augmenting glucose uptake in the peripheral tissues, chiefly muscle.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction
What the sources say
- Not checked yetcites [2] Shaw RJ, Lamia KA, Vasquez D: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005, 310: 1642-1646. 10.1126/science.1120781. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The benefits of metformin were primarily observed in patients <60 years old (RR 0.66) and in patients with a BMI greater than 35 kg/m2 (RR 0.47) [7] (Table 1).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [7] Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002, 346: 393-403. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A meta-analysis of 27 randomized trials showed that thiazolidinediones, sulfonylureas, and glinides were associated with weight gain; glucagon-like peptide-1 analogs, glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were associated with weight loss or no weight change.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in combination therapy
What the sources say
- Not checked yetcites [22] Phung OJ, Scholle JM, Talwar M, Coleman CI: Effect of noninsulin Antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010, 303 (14): 1410-1418. 10.1001/jama.2010.405. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Chinese individuals have a lower prevalence of diabetes and are less insulin resistant than Indians, so the results of the Chinese study may not be applicable to Asian Indian individuals [13].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [13] Pan XR, Li GW, Hu YH: Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Qing IGT and Diabetes Study. Diabetes Care. 1997, 20: 537-544. 10.2337/diacare.20.4.537. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Rosiglitazone was associated with more weight gain, edema, and greater durability of glycemic control; metformin was associated with a higher incidence of gastrointestinal events and glibenclamide with a higher risk of hypoglycaemia. [34].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and thiazolinediones
What the sources say
- Not checked yetcites [34] Scheen AJ: ADOPT study: which first-line glucose-lowering oral medication in type 2 diabetes?. Rev Med Liege. 2007, 62 (1): 48-52.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The glimepiride/metformin combination results in a lower HbA1c concentration and fewer hypoglycemic events when compared to the glibenclamide/metformin combination [25].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and sulfonylureas
What the sources say
- Not checked yetcites [25] González-Ortiza M, Guerrero-Romero J, Violante-Ortiz R: Efficacy of glimepiride/metformin combination versus glibenclamide/metformin in patients with uncontrolled type 2 diabetes mellitus. J Diabetes Complications. 2009, 23: 376-379. 10.1016/j.jdiacomp.2008.09.002. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The addition of rosiglitazone to metformin in a 24-week randomized, double-blind, parallel-group study significantly decreased HbA1c concentration and improved insulin sensitivity and HOMA ß cell function [32].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and thiazolinediones
What the sources say
- Not checked yetcites [32] Bailey CJ, Bagdonas A, Rubes J: Rosiglitazone-metformin fixed-dose combination compared with uptritrated metformin alone in type diabetes mellitus:a 24 week, multicenter, randomized, double-blind, parallel-group study. Clin Ther. 2005, 27: 1548-1561. 10.1016/j.clinthera.2005.10.012. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“IGT is highly prevalent in native Asian Indians. This population has several unique features such as a young age of diabetes onset and lower BMI along with high rates of insulin resistance and lower thresholds for diabetic risk factors [12].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
What the sources say
- Not checked yetcites [12] Ramachandran A, Snehalatha C, Vijay V: Low risk threshold for acquired diabetogenic factors in Asian Indians. Diab Res Clin Pract. 2004, 65: 189-195. 10.1016/j.diabres.2004.03.012. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“All noninsulin antidiabetic drugs when added to maximal metformin therapy are associated with similar HbA1c reduction but with varying degrees of weight gain and hypoglycemia risk.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in combination therapy
What the sources say
- Not checked yetcites [22] Phung OJ, Scholle JM, Talwar M, Coleman CI: Effect of noninsulin Antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010, 303 (14): 1410-1418. 10.1001/jama.2010.405. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Current guidelines from the American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) and the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) recommend early initiation of metformin as a first-line drug for monotherapy and combination therapy for patients with T2DM.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in the management of adult diabetic patients
What the sources say
- Not checked yetcites [16] American Diabetes Association: Summary of revisions to the 2011 clinical practice recommendations. Diabetes Care. 2011, 34 (Suppl 1): S3-
- Not checked yetcites [17] Rodbard HW, Jellinger PS, Davidson JA: Statement by an American association of clinical endocrinologists/American college of endocrinology consensus panel on type 2 diabetes mellitus. An algorithm for glycemic control. Endocr Pract. 2009, 15 (6): 540-559. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The use of metformin was associated with reduced all-cause mortality and reduced cardiovascular mortality.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and sulfonylureas
What the sources say
- Not checked yetcites [26] Johnson JA, Majumdar SR, Simpson SH: Decreased mortality associated with the use of metformin compared with sulfonylurea Monotherapy in type 2 diabetes. Diabetes Care. 2002, 25: 2244-2248. 10.2337/diacare.25.12.2244. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Metformin as added to insulin-based regimens has been shown to improve glycemic control, limit changes in body weight, reduce hypoglycemia incidence, and to reduce insulin requirements (sparing effect), allowing a 15–25% reduction in total insulin dosage [28,29].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and insulin
What the sources say
- Not checked yetcites [28] Giugliano D, Quatraro A, Consoli G: Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors. Eur J Clin Pharmacol. 1993, 44: 107-112. 10.1007/BF00315466. source
- Not checked yetcites [29] Lund SS, Tarnow L, Frandsen M: Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. BJ. 2009, 339: b4324-10.1136/bmj.b4324. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin’s first-line position was strengthened by the United Kingdom Prospective Diabetes Study (UKPDS) observation that the metformin-treated group had risk reductions of 32% (p = 0.002) for any diabetes-related endpoint, 42% for diabetes-related death (p = 0.017), and 36% for all-cause mortality (p = 0.011) compared with the control group.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin in the management of adult diabetic patients
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin has been shown to reduce insulin dose requirement (5.7–10.1 U/day), HbA1c (0.6–0.9%), weight (1.7–6.0 kg), and total cholesterol (0.3–0.41 mmol/l) [30].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin use in childhood and adolescence
What the sources say
- Not checked yetcites [30] Vella S, Buetow L, Royle P: The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010, 53 (5): 809-820. 10.1007/s00125-009-1636-9. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin is associated with short-term weight loss, improvement of insulin sensitivity, and decreased visceral fat [59].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin indications for management of obesity, insulin resistance, and non-alcoholic fatty liver in children and adolescents
What the sources say
- Not checked yetcites [59] Reinehr T, Kiess W, Kappellen T, Andler W: Insulin sensitivity among obese children and adolescents, according to degree of weight loss. Pediatrics. 2004, 114: 1569-1573. 10.1542/peds.2003-0649-F. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The PRESTO trial showed significant reductions of any clinical event (28%), myocardial infarction (69%), and all-cause mortality (61%) [74].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [74] Kao J, Tobis J, Mc Clelland RL: Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004, 93: 1347-1350. 10.1016/j.amjcard.2004.02.028. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The Metformin in Gestational Diabetes (MiG) trial, found no significant difference in the composite fetal outcome (composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score <7, or prematurity) between metformin and insulin. Women assigned to metformin had more preterm births and less weight gain compared to those in the insulin group [46].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pregnancy
What the sources say
- Not checked yetcites [46] Rowan JA, Hague WM, Gao W, Battin MR, Moore MP: MiG trial investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008, 358: 2003-2015. 10.1056/NEJMoa0707193. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It had statistically significant reductions in the risk of all-cause mortality, diabetes-related mortality (p = 0.017), and any end-point related to diabetes (p = 0.002), but not in myocardial infarction (p = 0.052) [18].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin has also been found to increase plasma GLP-1 levels, probably by either direct inhibition of DPPIV or by increased secretion, leading to reduced food intake and weight loss [40].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and incretin-based therapies
What the sources say
- Not checked yetcites [40] Mannucci E, Ognibene A, Cremasco F: Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care. 2001, 24: 489-494. 10.2337/diacare.24.3.489. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“When compared to glimepiride (1–8 mg once daily), metformin (500–1000 mg twice daily) lowered HbA1c to <7%, similar to glimepiride, but was associated with significantly less weight gain.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin use in childhood and adolescence
What the sources say
- Not checked yetcites [52] Gottschalk M, Danne T, Vlajnic A, Cara J: Glimepiride Versus Metformin as Monotherapy in Pediatric Patients With Type 2 Diabetes.A randomized, single-blind comparative study. DiabetesCare. 2007, 30: 790-794.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Diabetic patients are at high risk of cardiovascular events, particularly of coronary heart disease by about 3-fold [67,68].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [67] Kannel WB, McGee DL: Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham Study. Diabetes Care. 1979, 2: 120-126. 10.2337/diacare.2.2.120. source
- Not checked yetcites [68] Wingard DL, Barrett-Connor E: NationalDiabetes Data Group. Diabetes in America. Heart disease and diabetes. 1995, Washington, D.C: GPO, 429-48. NIH publication no.95-1468, 2
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The UKPDS pos-trial reported significant and persistent risk reductions for any diabetes-related end point (21%, p = 0.01), myocardial infarction (33%, p = 0.005), and death from any cause (27%, p = 0.002) [73].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [73] Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA: 10-year follow up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008, 359: 1577-1589. 10.1056/NEJMoa0806470. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent meta-analysis suggested that the cardiovascular effects of metformin could be smaller than had been hypothesized on the basis of the UKPDS; however, its results must be interpreted with caution given the low number of randomized controlled trials included [77].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [77] Boussageon R, Supper I, Bejan-Angoulvant T: Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med. 2012, 9 (4): e1001204-10.1371/journal.pmed.1001204. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Metformin may not be as effective as behavioral interventions in reducing BMI and when compared with drugs that are licensed for obesity, its effects are moderate [66].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin indications for management of obesity, insulin resistance, and non-alcoholic fatty liver in children and adolescents
What the sources say
- Not checked yetcites [66] Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O’Malley C, Stolk RP, Summerbell CD: Interventions for treating obesity in children. Cochrane Database Syst Rev. 2009, CD001872-1 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A retrospective analysis of patients databases in Saskatchewan, Canada reported significant reductions for all-cause mortality and cardiovascular mortality of 40% and 36%, respectively [26].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [26] Johnson JA, Majumdar SR, Simpson SH: Decreased mortality associated with the use of metformin compared with sulfonylurea Monotherapy in type 2 diabetes. Diabetes Care. 2002, 25: 2244-2248. 10.2337/diacare.25.12.2244. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It has been stated that type 2 diabetic patients without a previous history of myocardial infarction have the same risk of coronary artery disease (CAD) as non-diabetic subjects with a history of myocardial infarction [69].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
What the sources say
- Not checked yetcites [69] Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998, 339: 229-234. 10.1056/NEJM199807233390404. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The risk of developing cardiac heart failure (CHF) in diabetic individuals nearly doubles as the population ages [77].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [77] Boussageon R, Supper I, Bejan-Angoulvant T: Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med. 2012, 9 (4): e1001204-10.1371/journal.pmed.1001204. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The US Food and Drug Administration removed the heart failure contraindication from the packaging of metformin although a strong warning for the cautious use of metformin in this population still exists [80].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [80] Food and Drug Administration. Product label approval: metformin. 2006, http://packageinserts.bms.com/pi/piglucophage.pdf ,
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent review concluded that CHF could not be considered an absolute contraindication for metformin use and also suggest its protective effect in reducing the incidence of CHF and mortality in T2DM [83].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [83] Papanas N, Maltezos E, Mikhailidis DP: Metformin and heart failure: never say never again. Expert Opin Pharmacother. 2012, 1: 1-8. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The UKPDS recruited patients with newly diagnosed type 2 diabetes and demonstrated that tight glycemic control has beneficial effects on microvascular end points. However, it failed to show improvements in macrovascular outcomes.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Beyond glycemic control
What the sources say
- Not checked yetcites [18] Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352 (9131): 854-865. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mather et al. reported that metformin has no effect on endothelium dependent blood flow but has a significant effect on endothelium independent blood flow and insulin resistance reduction [89].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on endothelial function
What the sources say
- Not checked yetcites [89] Mather KJ, Verma S, Anderson TJ: Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001, 37 (5): 1344-1350. 10.1016/S0735-1097(01)01129-9. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several retrospective studies in patients with CHF and diabetes reported lower risk of death from any cause [81-83], lower hospital readmissions for CHF [81], and hospitalizations for any cause [81,82].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and heart failure
What the sources say
- Not checked yetcites [81] Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM: Thiazolinediones, metformin, and outcomes in older patients with diabetes and heart failure. Circulation. 2005, 111: 583-590. 10.1161/01.CIR.0000154542.13412.B1. source
- Not checked yetcites [82] Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA: Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005, 28: 2345-2351. 10.2337/diacare.28.10.2345. source
- Not checked yetcites [83] Papanas N, Maltezos E, Mikhailidis DP: Metformin and heart failure: never say never again. Expert Opin Pharmacother. 2012, 1: 1-8. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Conversely, Vitale et al. found significant improvement of endothelium dependent flow without a significant effect on endothelium independent response [90].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on endothelial function
What the sources say
- Not checked yetcites [90] Vitale C, Mercuro G, Cornoldi A, Fini M: Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med. 2005, 258: 250-256. 10.1111/j.1365-2796.2005.01531.x. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Metformin has been proposed to cause a mild and transient inhibition of mitochondrial complex I which decreases ATP levels and activates AMPK-dependent catabolic pathways [100], increasing lipolysis and ß-oxidation in white adipose tissue [102] and reducing neoglucogenesis [2].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on oxidative stress
What the sources say
- Not checked yetcites [100] Faure P, Rossini E, Wiernsperger N: An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Diabetes. 1999, 48: 353-357. 10.2337/diabetes.48.2.353. source
- Not checked yetcites [102] Anedda A, Rial E, Gonzalez Barroso : Metformin induces oxidative stress in white adipocytes and raises uncoupling proten levels. J Endocrinol. 2008, 199: 33-40. 10.1677/JOE-08-0278. source
- Not checked yetcites [2] Shaw RJ, Lamia KA, Vasquez D: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005, 310: 1642-1646. 10.1126/science.1120781. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It reduces reactive oxygen species (ROS) by inhibiting mitochondrial respiration [100] and decreases advanced glycosylation end product (AGE) indirectly through reduction of hyperglycemia and directly through an insulin-dependent mechanism [101].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on oxidative stress
What the sources say
- Not checked yetcites [100] Faure P, Rossini E, Wiernsperger N: An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Diabetes. 1999, 48: 353-357. 10.2337/diabetes.48.2.353. source
- Not checked yetcites [101] Beisswenger P, Rugiero-Lopez D: Metformin inhibition of glycation processes. Diabetes Metab. 2003, 29 (6S): 95-103.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The authors suggested that this action could be mediated by histone deacetylase sirtuin 1 (SIRT-1), a multifunctional protein involved in many intracellular pathways related to metabolism, stress response, cell cycle, and aging [103].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on oxidative stress
What the sources say
- Not checked yetcites [103] Zheng Z, Chen H, Li J, Li T, Zheng B, Zheng Y, Jin H, He Y, Gu Q, Xun X: Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin. Diabetes. 2012, 61 (1): 217-228. 10.2337/db11-0416. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The activated protein kinase (AMPK) forms a molecular hub for cellular metabolic control [122].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [122] Santomauro Júnior AC, Ugolini MR, Santomauro AT, Souto RP: Metformina e AMPK: Um Antigo Fármaco e Uma Nova Enzima no Contexto da Síndrome Metabólica. Arq Bras Endocrinol Metabol. 2008, 52 (1): 120-125. 10.1590/S0004-27302008000100017. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A significant decrease in TSH (P < 0.001) without reciprocal changes in any thyroid function parameter in diabetic patients had also been reported but only in hypothyroid subjects, not in euthyroid ones [113].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on thyroid function
What the sources say
- Not checked yetcites [113] Capelli C, Rotondi M, Pirola I, Agosti B, Gandossi E: TSH-lowering effect of metformin in type 2 diabetic patients differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care. 2009, 32: 1589-1590. 10.2337/dc09-0273. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Oxidative stress has been implicated in a variety of neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis disease [126].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [126] Detaille D, Guigas B, Chauvin C: Metformin prevents high glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process. Diabetes. 2005, 54: 2179-2187. 10.2337/diabetes.54.7.2179. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Nucleoside reverse transcriptase inhibitors (NRTIs), particularly thymidine analogues (zidovudine and stavudine), have been associated with morphological changes, particularly extremity fat loss [116]”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [116] Moyle GJ, Sabin CA, Cartledge J: A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. Acquir Immune Defic Syndr. 2006, 20: 2043-2050.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Metformin is associated with improvements in lipoprotein metabolism, including decreases in LDL-C [95], fasting and postprandial TGs, and free fatty acids [106].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects on lipid profile
What the sources say
- Not checked yetcites [95] Glueck CJ, Fontaine RN, Wang P: Metformin reduces weight, centripetalobesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001, 50: 856-861. 10.1053/meta.2001.24192. source
- Not checked yetcites [106] Eleftheriadou I, Grigoropoulou P, Katsilambros N, Tentolouris N: The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism. Curr Diabetes Rev. 2008, 4: 340-356. 10.2174/157339908786241133. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lipodystrophy, characterized by morphological (peripheral lipoatrophy, localized fat accumulation) and metabolic changes (hyperlipidemia, insulin resistance and hyperglycemia), is highly prevalent in patients on highly active antiretroviral therapy (HAART), occurring in 40% to 80% of patients [115].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [115] Kinlaw WB, Marsh B: Adiponectin and HIV-lipodystrophy:taking HAART. Endocrinology. 2004, 145: 484-486. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Favorable effects on insulin levels [98], insulin sensitivity [119], weight [97], flow-mediated vasodilation [119], and lipid profiles [98,119] have also been described.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and HIV lypodystrofy
What the sources say
- Not checked yetcites [98] Sheth S, Larson L: The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. BMC Infect Dis. 2010, 10: 183-10.1186/1471-2334-10-183. source
- Not checked yetcites [119] van Wijk , de Koning E, Castro M: Comparison of Rosiglitazone and Metformin for treating HIV Lipodistrophy. Ann Inter Med. 2005, 143: 337-346. source
- Not checked yetcites [97] Hadigan C, Corcoran C, Basgoz N: Metformin in the Treatment of HIV Lipodystrophy Syndrome A Randomized Controlled Trial. JAMA. 2000, 284: 472-477. 10.1001/jama.284.4.472. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A prospective study (median follow-up time of 9.6 years) found that metformin use at baseline was associated with lower cancer-related mortality and that this association appeared to be dose dependent [138].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [138] Landman GW, Kleefstra N, van Hateren KJ: Metformin associated with lower cancer mortality in type 2 diabetes ZODIAC-16. Diabetes Care. 2010, 33: 322-326. 10.2337/dc09-1380. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The underlying mechanisms of tumorigenesis in T2DM seem to be related to insulin resistance, hyperinsulinemia, elevated levels of IGF-1 [140-142], and hyperglycemia with the latter driving ATP production in cancer cells through the glycolytic pathway, a mechanism known as the Warburg effect [142].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [140] Inoue M, Iwasaki M, Otami T: Diabetes mellitus and the risk of cancer. Results from a large-scale population-based cohort study. Arch Intern Med. 2006, 166: 1871-1877. 10.1001/archinte.166.17.1871. source
- Not checked yetcites [141] Grimberg A, Cohen P: Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol. 2000, 183: 1-9. 10.1002/(SICI)1097-4652(200004)183:1<1::AID-JCP1>3.0.CO;2-J. source
- Not checked yetcites [142] Smith U, Gale EAU: Cancer and diabetes: are we ready for prime time?. Diabetologia. 2010, 53: 1541-1544. 10.1007/s00125-010-1815-8. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin significantly reduces tumorigenesis and cancer cell growth although how it does it is not well understood.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [133] Papanas N, Maltezos E, Mikhailidis DP: Metformin and cancer: licence to heal?. Expert Opin Investig Drugs. 2010, 19: 913-917. 10.1517/13543784.2010.499122. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Insulin has been shown to regulate a wide range of processes in the central nervous system such as food intake, energy homeostasis, reproduction, sympathetic activity, learning and memory [129], as well as neuronal proliferation, apoptosis, and synaptic transmission [130].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [129] Gupta A, Bisht B, Dey CS: Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like change. Neuropharmacology. 2011, 60: 910-920. 10.1016/j.neuropharm.2011.01.033. source
- Not checked yetcites [130] Selkoe DJ: The cell biology of ßamyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol. 1998, 8: 447-453. 10.1016/S0962-8924(98)01363-4. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“However, when insulin is added to metformin, it potentiates insulin’s effects on amyloid reduction, improves neuronal insulin resistance, and impairs glucose uptake and AD-associated neuropathological characteristics by activating the insulin signaling pathway [129].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [129] Gupta A, Bisht B, Dey CS: Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like change. Neuropharmacology. 2011, 60: 910-920. 10.1016/j.neuropharm.2011.01.033. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The mTOR is a key integrator of growth factor and nutrient signals as well as a critical mediator of the PI3K/PKB/Akt pathway, one of the most frequently disregulated signaling pathways in human cancer [144].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [144] Kalender A, Selvaraj A, Kim SY: Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPasedependent manner. Cell Metab. 2010, 11: 390-401. 10.1016/j.cmet.2010.03.014. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many studies showed reduced incidence of different types of cancer in patients as well a reduced cancer-related mortality in patients using metformin (Table 3).”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It may be due to its effects on insulin reduction and hyperinsulinemia, and consequently on IGF-1 levels, which have mitogenic actions enhancing cellular proliferation,but may also involve specific AMPK-mediated pathways [133].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [133] Papanas N, Maltezos E, Mikhailidis DP: Metformin and cancer: licence to heal?. Expert Opin Investig Drugs. 2010, 19: 913-917. 10.1517/13543784.2010.499122. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin has been shown to promote rodent and human neurogenesis in culture by activating a protein kinase C-CREB binding protein (PKC-CBP) pathway, recruiting neural stem cells and enhancing neural function, particularly spatial memory function.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and neuroprotection
What the sources say
- Not checked yetcites [132] Wang J, Gallagher D, De Vito L: Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell. 2012, 11: 23-35. 10.1016/j.stem.2012.03.016. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“When compared to those on other treatments, metformin users had a lower risk of cancer. A dose-relationship has been reported [138,144,145].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Future roles for metformin in cancer therapy
What the sources say
- Not checked yetcites [138] Landman GW, Kleefstra N, van Hateren KJ: Metformin associated with lower cancer mortality in type 2 diabetes ZODIAC-16. Diabetes Care. 2010, 33: 322-326. 10.2337/dc09-1380. source
- Not checked yetcites [144] Kalender A, Selvaraj A, Kim SY: Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPasedependent manner. Cell Metab. 2010, 11: 390-401. 10.1016/j.cmet.2010.03.014. source
- Not checked yetcites [145] Evans J, Donelly L, Emslie A: Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005, 330 (7503): 1304-1305. 10.1136/bmj.38415.708634.F7. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“About 10–30% of patients who are prescribed metformin have evidence of reduced vitamin B12 absorption due to calcium-dependent ileal membrane antagonism, an effect that can be reversed with supplemental calcium [166].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [166] Bauman WA, Shaw S, Jayatilleke E: Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000, 23: 1227-1231. 10.2337/diacare.23.9.1227. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several reports in literature related an increased risk of lactic acidosis with biguanides, mostly phenformin, with an event rate of 40–64 per 100,000 patients years [159] whereas the reported incidence with metformin is 6.3 per 100,000 patients years [160].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin contraindications
What the sources say
- Not checked yetcites [159] Rosand J, Friedberg J, Yang J: Fatal phenformin-associated lactic acidosis. Ann Intern Med. 1997, 127: 170- source
- Not checked yetcites [160] Salpeter SR, Greyber E, Pasternak GA, Salpeter EE: Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010, 1: CD002967-
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, as much as 5% of patients do not tolerate even the lowest dose [165].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [165] Cusi K, DeFronzo RA: Metformin: a review of its metabolic effects. Diabetes Rev. 1998, 6: 89-131.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Other adverse reactions are sporadic, such as leucocytoclastic vasculitis, allergic pneumonitis [170], cholestatic jaundice [171], and hemolytic anaemia [172].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [170] Klapholz L, Leitersdorf E, Weinrauch L: Leucocytoclastic vasculitis and pneumonitis induced by metformin. BMJ. 1986, 293: 483- source
- Not checked yetcites [171] Desilets DJ, Shorr AF, Moran KA, Holtzmuller KC: Cholestatic jaundice associated with the use of metformin. Am J Gastroenterol. 2001, 96: 2257-2258. 10.1111/j.1572-0241.2001.03972.x. source
- Not checked yetcites [172] Kashyap AS, Kashyap S: Haemolytic anaemia due to metformin. Postgrad Med J. 2000, 76: 125-126. 10.1136/pmj.76.892.125. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This vitamin B12 deficiency is rarely associated with megaloblastic anemia [167].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [167] Callaghan TS, Hadden DR, Tomkin GH: Megaloblastic anemia due to vitamin B12 malaborsption associated with long-term metformin treatment. Br Med J. 1980, 280: 1214-1215. 10.1136/bmj.280.6225.1214. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Vitamin B12 deficiency has been related with dose and duration of metformin use and occurs more frequently among patients that use it for more than 3 years and in higher doses [169].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [169] Wei Ting RZ, Szeto CC, Chan M, Ma K: Risk Factors of Vitamin B12 Deficiency in Patients Receiving Metformin. Arch Intern Med. 2006, 166: 1975-1979. 10.1001/archinte.166.18.1975. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Some of these mechanisms may be through inhibition of cell growth [148], IGF-1 signaling [149], inhibition of the mTOR pathway [150], reduction of human epidermal growth factor receptor type 2 (HER-2) expression (a major driver of proliferation in breast cancer) [151], inhibition of angiogenesis and inflammation [152], induction of apoptosis and protein 53 (p53) activation [153], cell cycle arrest”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
What the sources say
- Not checked yetcites [148] Ben Sahra I, Laurent K, Loubat A: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 2008, 27: 3576-3586. 10.1038/sj.onc.1211024. source
- Not checked yetcites [149] Pollak M: Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer. 2008, 8: 915-928. 10.1038/nrc2536. source
- Not checked yetcites [150] Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 2006, 66: 10269-10273. 10.1158/0008-5472.CAN-06-1500. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Frid et al. supports these recommendations through findings that above 30 ml/min/1.73 m2 metformin levels rarely goes above 20 mmol/l, which seems to be a safe level [163].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin contraindications
What the sources say
- Not checked yetcites [163] Frid A, Sterner GN, Londahl M: Novel assay of metformin levels in patients with type 2 diabetes mellitus and varying levels of renal function. Diabetes Care. 2010, 33: 1291-1293. 10.2337/dc09-1284. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These effects are generally transient, arise early in the course of treatment, and tend to subside over time [176].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Tolerability
What the sources say
- Not checked yetcites [176] Haupt E, Knick B, Koschinsky T, Liebermeister H, Schneider J, Hirche H: Oral antidiabetic combination therapy with sulphonylureas and metformin. Diabete Metab. 1991, 17: 224-231.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Metformin XR has been associated with improved tolerability [182] and increased compliance [183].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin XR
What the sources say
- Not checked yetcites [182] Raz I, Delaet I, Goyvaerts H: Safety and efficacy of novel extended-release formulation of metformin in patients with type 2 diabetes. Diabetes. 2000, 49 (Suppl 1): A363-
- Not checked yetcites [183] Donnelly LA, Morris AD, Pearson ER: Adherence in patients transferred from immediate release metformin to a sustained release formulation: a population-based study. Diabetes Obes Metab. 2009, 11: 338-342. 10.1111/j.1463-1326.2008.00973.x. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In recent years, metformin has become the first-line therapy for patients with type 2 diabetes.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Gastrointestinal side-effects are common with the use of metformin of standard release and are usually associated with rapid titration and high-dose initiation of metformin.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Tolerability
What the sources say
- Not checked yetcites [176] Haupt E, Knick B, Koschinsky T, Liebermeister H, Schneider J, Hirche H: Oral antidiabetic combination therapy with sulphonylureas and metformin. Diabete Metab. 1991, 17: 224-231.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hypoglycemia is very uncommon with metformin monotherapy [173] but has been reported in combination regimens [174], likely due to metformin potentiating other therapeutic agents.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Adverse effects
What the sources say
- Not checked yetcites [173] Giugliano D, De Rosa N, Di Maro G: Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care. 1993, 16: 1387-1390. 10.2337/diacare.16.10.1387. source
- Not checked yetcites [174] United Kingdom Prospective Diabetes Study (UKPDS) Group: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years (UKPDS 13). BMJ. 1995, 310: 83-88. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“No significant differences were observed by any anthropometric, clinical, or laboratory measures except for plasma triglycerides which were lower in the group switched to metformin XR [181].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin XR
What the sources say
- Not checked yetcites [181] Levy J, Cobas RA, Gomes MB: Assessment of efficacy and tolerability of oncedaily extended release metformin in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2010, 2: 16-10.1186/1758-5996-2-16. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The metformin XR formulation releases the active drug through hydrated polymers which expand after uptake of fluid, prolonging gastric residence time which leads to slower drug absorption in the upper gastrointestinal tract and allows once-daily administration [180].”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin XR
What the sources say
- Not checked yetcites [180] Donahue S, Marathe P, Guld T, Meeker J: The phamacokinetics and pharmacodynamics of extended-release metformin tablets vs immediate-release metformin in subjects with type 2 diabetes. Diabetes. 2002, 51 (Suppl 2): A468-
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metformin tolerability as well as patient acceptance was greater in the group switched to metformin XR.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin XR
What the sources say
- Not checked yetcites [181] Levy J, Cobas RA, Gomes MB: Assessment of efficacy and tolerability of oncedaily extended release metformin in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2010, 2: 16-10.1186/1758-5996-2-16. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus far, metformin is the only antidiabetic agent which has shown reduced macrovascular outcomes which is likely explained by its effects beyond glycemic control.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Conclusions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A large amount of evidence in literature supports its use even in cases where it would be contra-indicated mainly due to the fear of lactic acidosis which has been over-emphasized as the available data suggest that lactate levels and risk of lactic acidosis do not differ appreciably in patients taking this drug versus other glucose-lowering agents.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Conclusions
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Some cationic agents such as amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin that are eliminated by renal tubular secretion may compete with metformin for elimination.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Drug interactions
What the sources say
- Not checked yetcites [175] Glucophage® and Glucophage XRproduct information. Bristol-Myers Squibb Company. 2003, Available at: http://www.drugs.com/pro/glucophage.html
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Concomitant administration of cimetidine, furosemide, or nifedipine may also increase the concentration of metformin.”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Drug interactions
What the sources say
- Not checked yetcites [175] Glucophage® and Glucophage XRproduct information. Bristol-Myers Squibb Company. 2003, Available at: http://www.drugs.com/pro/glucophage.html
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Aggressive treatment is required in type 2 diabetes mellitus to achieve glycemic and cardiovascular risk factor goals.
“The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals.”
The paper relies on this without support.
Lifestyle modifications such as diet and exercise and switching antiretroviral therapies are of limited value in reducing visceral abdominal fat.
“Lifestyle modifications such as diet and exercise and switching antiretroviral therapies seems to be of limited value in reducing visceral abdominal fat (VAT).”
The paper relies on this without support.
Mitochondrial dysfunction has a pivotal role in oxidative stress.
“Mitochondrial dysfunction has a pivotal role in oxidative stress.”
The paper relies on this without support.
Renal dysfunction is the most common risk factor associated with lactic acidosis in patients using metformin.
“Renal dysfunction is the most common risk factor associated with lactic acidosis”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Metformin is a synthetic biguanide, orally effective and insulin sensitizing anti-diabetic drug, which for most patients is the first line anti-hyperglycemic for the treatment of type 2 diabetes mellitus (T2DM) (1).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [1]
In the citing paper
“In addition to its benefits as an anti-hyperglycemic agent, metformin also lowers the atherosclerotic burden in non-diabetic persons at risk of developing T2DM (1, 7).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [1]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and cancer
“| Evans [135] | Pilot Observational Study | Not specified | Tayside, Scotland. UK | 11,876 | 8 | IMC, smoking, blood pressure, material deprivation |”
§ Metformin: an old but still the best treatment for type 2 diabetes > References
“135. Li D Yeung SJ Hassan MM Konopleva M Abbruzzese JL Anti-diabetic therapies affect risk of pancreatic cancer”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
“| UKPDS 33 [18] | Prospective | 10 yr | Significant reduction in all-cause mortality, diabetes related mortality, and any end-point related to diabetes. |”
§ Metformin: an old but still the best treatment for type 2 diabetes > References
“18. Prospective Diabetes Study (UKPDS) Group Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Effects of metformin on vascular protection
“| Johnson et al.[24] | Retrospective | 9 yr | Reduction of all-cause mortality and of cardiovascular mortality |”
§ Metformin: an old but still the best treatment for type 2 diabetes > References
“24. Hanefeld M Brunetti P Schhernthaner GH One year glycemic control with sulphonylurea plus pioglitazone versus sulphonylurea plus metformin”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
“| IDPP [9] | yes | India | 522 | 3 | −26.4% | −28.2% |”
§ Metformin: an old but still the best treatment for type 2 diabetes > Introduction > Metformin and pre-diabetes
“The relative risk reduction was 28.5% with lifestyle modification (p = 0.018), 26.4% with metformin (p = 0.029), and 28.2% with lifestyle modification plus metformin (p = 0.022)”
Citations
Cites
1 retracted
Interventions for treating obesity in children
Oude Luttikhuis, H., Baur, L., Jansen, H., Shrewsbury, V. A., O'Malley, C., Stolk, R. P., & Summerbell, C. D. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001872.pub2 · Cited by 1,531
RetractedGrundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
Wild, S., Roglic, G., Green, A., Sicree, R., & King, H. (2004) · Diabetes Care · doi:10.2337/diacare.27.5.1047 · Cited by 15,297
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
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10-year follow-up of intensive glucose control in type 2 diabetes
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Metadata
- Authors
- Rojas, L. B. A., & Gomes, M. B.
- Affiliations
- Universidade do Estado do Rio de Janeiro (BR)
- Corresponding author
- Rojas, Lilian Beatriz Aguayo
- Venue
- Diabetology & Metabolic Syndrome
- Published
- 2013-02-15
- Volume
- 5
- Issue
- 1
- Pages
- 6-6
- ISSN
- 1758-5996 (ISSN-L)
- PMC
- PMC3607889
- OpenAlex
- W2119008227
- Semantic Scholar
- 8aecf912fff7c01ab9a5048ab405b159114ee63e
- Cited by
- 567
- References
- 194
- Citations by year
- 2026: 18 · 2025: 39 · 2024: 33 · 2023: 57 · 2022: 41 · 2021: 49 · 2020: 67 · 2019: 45 · 2018: 46 · 2017: 62 · 2016: 46 · 2015: 26 · 2014: 28 · 2013: 10
- FWCI
- 28.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Diabetology & Metabolic Syndrome (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metformin, type 2 diabetes, first-line therapy, glycemic control, cardiovascular risk reduction, insulin resistance, endothelial dysfunction, oxidative stress, hemostasis, lipid profile, fat redistribution, oral antidiabetic drugs, drug interactions, hypoglycemia, dose titration, sustained drug release, prediabetes, obesity, gestational diabetes mellitus, cancer, neuroprotection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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