The DOI matches its Crossref record; 293 of the 293 references it cites were found in a registry or an index; 3 of the 221 sources its claims cite were checked for support.
Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity
Open accessAbstract
&NA; Metformin is everywhere. Originally introduced in clinical practice as an antidiabetic agent, its role as a therapeutic agent is expanding to include treatment of prediabetes mellitus, gestational diabetes mellitus, and polycystic ovarian disease; more recently, experimental studies and observations in randomized clinical trials suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes mellitus and reviews the results of metaanalyses of metformin in gestational diabetes mellitus as well as the treatment of obese, non‐diabetic, pregnant women to prevent macrosomia. We highlight the results of a randomized clinical trial in which metformin administration in early pregnancy did not reduce the frequency of large‐for‐gestational‐age infants (the primary endpoint) but did decrease the frequency of preeclampsia (a secondary endpoint). The mechanisms by which metformin may prevent preeclampsia include a reduction in the production of antiangiogenic factors (soluble vascular endothelial growth factor receptor‐1 and soluble endoglin) and the improvement of endothelial dysfunction, probably through an effect on the mitochondria. Another potential mechanism whereby metformin may play a role in the prevention of preeclampsia is its ability to modify cellular homeostasis and energy disposition, mediated by rapamycin, a mechanistic target. Metformin has a molecular weight of 129 Daltons and therefore readily crosses the placenta. There is considerable evidence to suggest that this agent is safe during pregnancy. New literature on the role of metformin as a chemotherapeutic adjuvant in the prevention of cancer and in prolonging life and protecting against aging is reviewed briefly. Herein, we discuss the mechanisms of action and potential benefits of metformin.
Overview
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Written from the paper’s full text.
TL;DR
Metformin is a pleiotropic drug whose roles are expanding beyond diabetes to gestational diabetes, possible preeclampsia prevention, cancer risk reduction, and longevity. This narrative review summarizes historical, meta-analytic, randomized-trial, and mechanistic evidence, emphasizing mitochondrial and mTOR/nutrient-sensing pathways.
Key findings
- In gestational diabetes meta-analyses, metformin was superior to insulin for reducing maternal weight gain and gestational hypertension; Gui et al. found no change in large-for-gestational-age (LGA), small-for-gestational-age (SGA), hypoglycemia, or preeclampsia, while Butalia et al. reported significantly decreased neonatal hypoglycemia, LGA neonates, and neonatal intensive care unit admissions.
- Two UK randomized trials in obese non-diabetic pregnant women conflicted: EMPOWaR (BMI >30 kg/m²; metformin 500 mg titrated to a maximum tolerable dose ≤2,500 mg) had no significant effect on birth weight, maternal weight gain, preeclampsia, or combined adverse pregnancy outcomes; the Fetal Medicine Foundation trial (BMI >35 kg/m²; 1 g/day increased by 0.5 g/week to 3 g/day) did not reduce LGA but significantly reduced preeclampsia and maternal weight gain, though not gestational diabetes. The review attributes the discrepancy to differences in BMI, dose, compliance, and recruitment: 13% (443/3329) consented in EMPOWaR versus 47% (400/844) in the Fetal Medicine Foundation trial, and compliance was 67% versus almost 80% taking at least 50% of prescribed tablets.
- Proposed preeclampsia mechanisms include reduced production of anti-angiogenic factors sFlt-1/sVEGFR-1 and soluble endoglin, improved endothelial dysfunction, and effects on the mitochondrial electron transport chain, particularly complex I; metformin also modifies cellular nutrient sensing via AMPK and mTOR. Metformin has a molecular weight of 129 Da, crosses the placenta with a reported lag time of 1.7±0.28 minutes, and meta-analyses found no increased risk of congenital malformations.
- In cancer and aging, a meta-analysis reported that metformin-treated diabetic patients had a 31% reduction in cancer incidence and a 34% reduction in cancer mortality after adjusting for body mass index; metformin extended longevity in worms and mice but not Drosophila. The TAME trial is planned to test metformin in 3,000 subjects aged 65–79 years with a composite endpoint of cardiovascular events, cancer, dementia, and mortality.
Methods
- Narrative review, not a systematic review or meta-analysis; no primary data collection or new experimental study is reported.
- Synthesizes published literature on metformin history, gestational diabetes meta-analyses, randomized trials in obese non-diabetic pregnant women (EMPOWaR and the Fetal Medicine Foundation trial), mechanistic studies of preeclampsia, and evidence on cancer and aging.
- Main analysis is qualitative synthesis and mechanistic interpretation, drawing on meta-analyses, randomized trials, animal studies, and in vitro/ex vivo placental and vascular studies.
Limitations
- The paper does not state a formal limitations section.
- Evident from the text: it is a narrative review with selective citation rather than a systematic search or quantitative pooling, so it may not comprehensively capture all relevant evidence.
- Evident from the text: many mechanistic and causal claims are inferential, based on secondary literature, animal models, and in vitro findings, and the review does not independently verify the cited results.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
127 Not checked yet · 14 Own interpretation · 4 No basis given · 2 Partly supported · 2 Own result · 1 Supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There is excessive production of sVEGFR-1 and soluble endoglin in the uterus of preeclamptic patients(121) proportional to the severity of the disease (151–153)”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > The role of angiogenic and antiangiogenic factors in the genesis of preeclampsia
What the sources say
- Partly supportedcites [121] Bujold, 2005, Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin, J Matern Fetal Neonatal Med sourceExperimental — accuracy not yet measured
The Discussion concludes that excess circulating sVEGFR-1 in preeclampsia suggests increased uterine production, supporting that part of the claim. Our copy does not address soluble endoglin. The severity clause is attached to different citations (151–153), not this source; page numbers were not available in our copy. (LLM, conf=0.87)
- Not checked yetcites [151] Levine, 2004, Circulating angiogenic factors and the risk of preeclampsia, N Engl J Med source
- Not checked yetcites [152] Lai, 2014, Competing risks model in screening for preeclampsia by serum placental growth factor and soluble fms-like tyrosine kinase-1 at 30-33 weeks’ gestation, Fetal Diagn Ther source
- Not checked yetcites [153] Tsiakkas, 2016, Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30-34 weeks’ gestation, Am J Obstet Gynecol source
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
“Suboptimal compliance in randomized trials is well known to cause negative results(97–101).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Trial design and execution may explain the contradictory results of the two UK trials?
What the sources say
- Not checked yetcites [97] Cramer, 1991
- Partly supportedcites [98] Cramer, 2002, Effect of partial compliance on cardiovascular medication effectiveness, Heart sourceExperimental — accuracy not yet measured
The ‘Compliance and Outcomes’ section reports that effectiveness was greatly reduced among patients taking less than 70% of prescribed doses in the Helsinki heart study, and describes a dose–benefit relationship in another trial. It does not say that suboptimal compliance causes randomized trials to produce negative results; that trial-level conclusion goes beyond the passage. (LLM, conf=0.82)
- Not checked yetcites [99] Cramer, 2003, Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes, Value Health source
- Not checked yetcites [100] Cramer, 2008, Medication compliance and persistence: terminology and definitions, Value Health source
- Not checked yetcites [101] Shingler, 2014, Treatment preference, adherence and outcomes in patients with cancer: literature review and development of a theoretical model, Curr Med Res Opin source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“metformin was shown to extend longevity in worms(2) and mice(3) (although not in Drosophila(275)).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > A role for metformin in cancer and aging
What the sources say
- Supportedcites [3] Martin-Montalvo, 2013, Metformin improves healthspan and lifespan in mice, Nat Commun source
The Results section (“Metformin increases healthspan and longevity of mice”) reports that dietary metformin at 0.1% extended mean lifespan in male C57BL/6 mice by 5.83%. This supports the cited claim that metformin was shown to extend longevity in mice, though the effect was dose-dependent. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
In the paper
“Gui et al.(75) published a systematic review and meta-analysis in which metformin was shown to be superior to insulin in reducing maternal weight gain during pregnancy as well as in the frequency of gestational hypertension (Figure 5a,); however, metformin did not change the frequency of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) fetuses or of hypoglycemia and preeclampsia(”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Important results from the meta-analyses: metformin reduces the frequency of gestational hypertension in gestational diabetes
What the sources say
- Not checked yetcites [75] Gui, 2013, Metformin vs insulin in the management of gestational diabetes: a meta-analysis, PloS One 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We highlight the results of a randomized clinical trial in which metformin administration in early pregnancy did not reduce the frequency of large-for-gestational-age infants (primary endpoint), but did decrease the frequency of preeclampsia (a secondary endpoint).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Metformin has a molecular weight of 129 Dalton, and therefore, readily crosses the placenta.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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None of the sources cited for this claim have been checked yet.
In the paper
“reduction of glucose absorbtion by the gastro-intestinal tract(44, 45)”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present
What the sources say
- Not checked yetcites [44] Natali, 2006, Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review, Diabetologia source
- Not checked yetcites [45] Foretz, 2014, Metformin: from mechanisms of action to therapies, Cell Metab source
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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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 mechanisms by which metformin may prevent preeclampsia include a reduction in the production of anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 and soluble endoglin), and improving endothelial dysfunction, probably through an effect on the mitochondria.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
hedgedconditional- 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, metformin did not change the frequency of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) fetuses or of hypoglycemia and preeclampsia(75).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Important results from the meta-analyses: metformin reduces the frequency of gestational hypertension in gestational diabetes
What the sources say
- Not checked yetcites [75] Gui, 2013, Metformin vs insulin in the management of gestational diabetes: a meta-analysis, PloS One 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.
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 mechanisms by which metformin may prevent preeclampsia include a reduction in the production of anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 and soluble endoglin), and improving endothelial dysfunction, probably through an effect on the mitochondria.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
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. 31
- Probably not a substantial claim. 12
In the paper
“Butalia et al.(77) reported that, compared to insulin, metformin significantly decreased the frequency of neonatal hypoglycemia, LGA neonates, and admissions to a neonatal intensive care unit (Figure 5b,)(56, 72–74, 77–83).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Important results from the meta-analyses: metformin reduces the frequency of gestational hypertension in gestational diabetes
What the sources say
- Not checked yetcites [77] Butalia, 2017, Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis, Diabetic Med source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“There is considerable evidence suggesting that this agent is safe during pregnancy.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
hedged- 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
“however, metformin did not change the frequency of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) fetuses or of hypoglycemia and preeclampsia(75).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Important results from the meta-analyses: metformin reduces the frequency of gestational hypertension in gestational diabetes
What the sources say
- Not checked yetcites [75] Gui, 2013, Metformin vs insulin in the management of gestational diabetes: a meta-analysis, PloS One 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.
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
“Metformin has a molecular weight of 129 Dalton, and therefore, readily crosses the placenta.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
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.
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
“Another potential mechanism whereby metformin may play a role in the prevention of preeclampsia is its ability to modify cellular homeostasis and energy disposition, mediated by mTOR.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“Originally introduced in clinical practice as an anti-diabetic agent, its role as a therapeutic agent is expanding to include treatment of pre-diabetes, gestational diabetes, polycystic ovarian disease, and more recently, experimental studies, as well as observations in randomized clinical trials, suggest that metformin could have a place in the treatment or prevention of preeclampsia.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Abstract
hedgedconditional- 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
“Gui et al.(75) suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species, the two mechanisms implicated in the pathophysiology of preeclampsia(84–94).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Important results from the meta-analyses: metformin reduces the frequency of gestational hypertension in gestational diabetes
What the sources say
- Not checked yetcites [75] Gui, 2013, Metformin vs insulin in the management of gestational diabetes: a meta-analysis, PloS One source
- Not checked yetcites [84] Rodgers, 1988, Preeclampsia is associated with a serum factor cytotoxic to human endothelial cells, Am J Obstet Gynecol source
- Not checked yetcites [85] Roberts, 1989, Preeclampsia: an endothelial cell disorder, Am J Obstet Gynecol source
- Not checked yetcites [86] Myatt, 2009, Vascular biology of preeclampsia, J Thromb Haemost source
- Not checked yetcites [87] Myatt, 2000, Oxidative stress causes vascular dysfunction in the placenta, J Matern Fetal Med
- Not checked yetcites [88] Hubel, 1996, Decreased transferrin and increased transferrin saturation in sera of women with preeclampsia: implications for oxidative stress, Am J Obstet Gynecol source
- Not checked yetcites [89] Many, 1996, Hyperuricemia and xanthine oxidase in preeclampsia, revisited, Am J Obstet Gynecol source
- Not checked yetcites [90] Burton, 2004, Placental oxidative stress: from miscarriage to preeclampsia, J Soc Gynecol Investig source
- Not checked yetcites [91] Burton, 2009, Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia, Placenta source
- Not checked yetcites [92] Myatt, 2010, Review: reactive oxygen and nitrogen species and functional adaptation of the placenta, Placenta source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“By contrast, in the EMPOWaR trial, compliance was defined as ingestion of at least one tablet for at least 29% of the days between randomization and delivery, and only 67% of women fulfilled this criterion(95).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Trial design and execution may explain the contradictory results of the two UK trials?
What the sources say
- Not checked yetcites [95] Chiswick, 2015, Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial, Lancet Diabetes Endocrinol source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“Soluble endoglin is a cell surface co-receptor for transforming growth factor (TGF)-β1, which blocks TGF-β1–mediated activation of endothelial nitric oxide synthase (eNOS) and promotes vasorelaxation(124).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > The role of angiogenic and antiangiogenic factors in the genesis of preeclampsia
What the sources say
- Not checked yetcites [124] Venkatesha, 2006, Soluble endoglin contributes to the pathogenesis of preeclampsia, Nat Med source
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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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“that causes maternal plasma concentrations of sVEGFR-1 and soluble endoglin to increase before preeclampsia is diagnosed, making them potential biomarkers for the disease(111, 120, 128, 129, 132, 133, 137, 138, 154–179).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > The role of angiogenic and antiangiogenic factors in the genesis of preeclampsia
What the sources say
- Not checked yetcites [111] Chaiworapongsa, 2014, Pre-eclampsia part 2: prediction, prevention and management, Nat Rev Nephrol source
- Not checked yetcites [120] Chaiworapongsa, 2005, Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia, J Matern Fetal Neonatal Med source
- Not checked yetcites [128] Erez, 2008, The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age, J Matern Fetal Neonatal Med source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Importantly, transfection of cells with miR-210 resulted in a significant reduction in oxygen consumption by mitochondria, mitochondrial respiratory deficiency, and production of ROS(207).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [207] Muralimanoharan, 2012, MIR-210 modulates mitochondrial respiration in placenta with preeclampsia, Placenta 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
“Torbergsen et al. suggested that these women developed preeclampsia because their dysfunctional mitochondria could not meet the increased energy demands of pregnancy, and the failure of adequate cellular energy production led to an accumulation of ADP, which is able to mediate most of the changes seen in preeclampsia(89, 197)”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
hedgeddirectn = 10- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“while both early and late preeclampsia are associated with an elevated P/O ratio(208).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [208] Vishnyakova, 2016, Mitochondrial role in adaptive response to stress conditions in preeclampsia, Sci Rep source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Six of 10 women with a mitochondrial disease had at least one pregnancy complicated by preeclampsia or eclampsia, whereas none had been hypertensive in the non-pregnant state.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [196] Torbergsen, 1989, Pre-eclampsia: a mitochondrial disease?, Acta Obstet Gynecol Scand source
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Although the emphasis on the toxic factors produced by an ischemic placenta has been on the balance between angiogenic and anti-angiogenic factors, evidence now suggests that cytokines, such as TNF-α and IL-10, are altered in early and late preeclampsia, and the changes correlate with the type of histopathological changes in the placenta(185).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > The role of angiogenic and antiangiogenic factors in the genesis of preeclampsia
What the sources say
- Not checked yetcites [185] Weel, 2016, Association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia, PloS One source
hedgedcorrelational- 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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It may state two separate claims as one.
In the paper
“Thus, early-onset preeclampsia is associated with mitochondrial activation, up-regulation of OPA-1, active DNA replication (resulting from a high respiration rate), and TFAM down-regulation, while both early and late preeclampsia are associated with an elevated P/O ratio(208).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [208] Vishnyakova, 2016, Mitochondrial role in adaptive response to stress conditions in preeclampsia, Sci Rep source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“and these mitochondrial changes were not limited to uterine tissues, thus implying that mitochondrial dysfunction was a systemic disorder.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [198] Shanklin, 1990, Ultrastructural aspects of preeclampsia: II, mitochondrial changes, Am J Obstet Gynecol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Women with early-onset preeclampsia had 1) a two-fold increase in the mRNA expression of OPA (optic atrophy)-1 and a three-fold increase in OPA-1 protein expression (cleaved and uncleaved forms) in patients with early-onset preeclampsia.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [208] Vishnyakova, 2016, Mitochondrial role in adaptive response to stress conditions in preeclampsia, Sci Rep source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“the report also suggested that metformin regulates these anti-angiogenic factors at the level of the mitochondria.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > The role of angiogenic and antiangiogenic factors in the genesis of preeclampsia
What the sources say
- Not checked yetcites [20] Brownfoot, 2016, Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction, Am J Obstet Gynecol source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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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
“ADP is a vasoconstrictor, causes platelet aggregation, and breaks down to uric acid.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
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 placentas of patients with preeclampsia(204), as well as those from pregnancies with preeclampsia and SGA(205), overexpress the microRNA (miR)-210”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [204] Zhu, 2009, Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies, Am J Obstet Gynecol source
- Not checked yetcites [205] Pineles, 2007, Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia, Am J Obstet Gynecol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, it was demonstrated that miR-210 was induced by hypoxia, and RNA interference knockdown resulted in autophagosomal and siderosomal iron accumulation, implicating siderosis or interstitial trophoblasts as mechanisms in preeclampsia and SGA(206)”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [206] Lee, 2011, MiR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies, Am J Pathol source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This signaling system is highly expressed in the syncytiotrophoblast, and its activity is regulated by glucose and amino-acid concentrations(226, 227, 240).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > The mechanistic target of rapamycin (mTOR) translates maternal nutritional status via the placenta to the fetus
What the sources say
- Not checked yetcites [226] Roos, 2009, Placental mTOR links maternal nutrient availability to fetal growth, Biochem Soc Trans source
- Not checked yetcites [227] Rosario, 2013, Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells, J Physiol source
- Not checked yetcites [240] Lager, 2012, Regulation of nutrient transport across the placenta, J Pregnancy
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nutrient sensing occurs through several pathways(225), the most important of which are: the AMPK pathway, which is a global energy sensor in cells;glycogen synthase 3 (GSK-3), which acts as a glucose sensor;the hexose-amino signaling pathway, which depends on the availability of nutrients such as glucose, glutamine, and acetyl-CoA;the amino-acid response signal transduction pathway, which is activ”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > Fetal-placental nutritient sensing
What the sources say
- Not checked yetcites [225] Jansson, 2013, Role of placental nutrient sensing in developmental programming, Clin Obstet Gynecol source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, succinate is also an inhibitor of HIF-1α(213), which has been implicated in the exaggerated production of sFlt-1 and in the pathophysiology of preeclampsia(214, 215)”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [213] Selak, 2005, Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase, Cancer Cell source
- Not checked yetcites [214] Kanasaki, 2008, Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia, Nature source
- Not checked yetcites [215] Tal, 2012, The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis, Biol Reprod source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Rapamycin acts by interacting with a family of TOR molecules that is highly-conserved functionally and evolutionarily from yeast to humans, and it contains two multiprotein complexes that are functionally and structurally different: the first, mTORC1, is rapamycin-sensitive; and the second, mTORC2, is rapamycin-resistant(237).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > The mechanistic target of rapamycin (mTOR) translates maternal nutritional status via the placenta to the fetus
What the sources say
- Not checked yetcites [237] Aylett, 2016, Architecture of human mTOR complex 1, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Nutrient sensing is a crucial requirement for fetal development.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > Fetal-placental nutritient sensing
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Brownfoot et al.(20) found that metformin can improve endothelial dysfunction, reduce the expression of vascular adhesion molecule 1 mRNA induced by TNFα, and improve whole-blood vessel angiogenesis impaired by sFlt-1 or sVEGFR-1.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
What the sources say
- Not checked yetcites [20] Brownfoot, 2016, Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction, Am J Obstet Gynecol source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Rapamycin can also prolong the life cycle of many species as diverse as worms and mice, and its signaling system has been implicated as the master regulator of cellular growth and metabolism.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > The mechanistic target of rapamycin (mTOR) translates maternal nutritional status via the placenta to the fetus
What the sources say
- Not checked yetcites [230] Zoncu, 2011, mTOR: from growth signal integration to cancer, diabetes and ageing, Nat Rev Mol Cell Biol source
- Not checked yetcites [231] Hirota, 2011, Heightened uterine mammalian target of rapamycin complex 1 (mTORC1) signaling provokes preterm birth in mice, Proc Natl Acad Sci U S A source
- Not checked yetcites [232] Shimobayashi, 2014, Making new contacts: the mTOR network in metabolism and signalling crosstalk, Nat Rev Mol Cell Biol source
- Not checked yetcites [233] Kim, 2015, MTOR: a pharmacologic target for autophagy regulation, J Clin Invest source
- Not checked yetcites [234] Deng, 2016, P53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing, J Clin Invest source
- Not checked yetcites [235] Kennedy, 2016, The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging, Cell Metab source
- Not checked yetcites [236] Xie, 2016, MTOR inhibitors in cancer therapy, F1000Res source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Both complexes control cell growth and metabolism in response to the availability of nutrients, energy, and growth factors.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > The mechanistic target of rapamycin (mTOR) translates maternal nutritional status via the placenta to the fetus
What the sources say
- Not checked yetcites [237] Aylett, 2016, Architecture of human mTOR complex 1, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“mTOR has key properties in the placenta(225, 226) that include its activation by insulin, IGF-1, and leptin, and its inhibition by cortisol.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > The mechanistic target of rapamycin (mTOR) translates maternal nutritional status via the placenta to the fetus
What the sources say
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.
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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
“The key structure in the placenta responsible for nutritient sensing is the syncytiotrophoblast, which covers the villous tree and is in direct contact with the maternal blood in the intervillous space.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > The biological basis for the effects of metformin on fetal growth > Fetal-placental nutritient sensing
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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 changes in the mitochondrial function in preeclampsia suggest there are perturbations in the cellular energy balance of patients with this syndrome that affect cell growth and division (especially in the placenta and the fetus); all are modified by metformin.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Mechanisms by which metformin may prevent preeclampsia > Preeclampsia as a mitochondrial disorder and the effect of metformin on mitochondrial function
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and is currently classified as category B in the United States and as category C in Australia (247, 248).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Safety of metformin during pregnancy
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Nucleocytoplasmic shuttling regulates mTORC activity, an effect that can be reversed by RNA silencing.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > A role for metformin in cancer and aging
What the sources say
- Not checked yetcites [278] Wu, 2016, An ancient, unified mechanism for metformin growth inhibition in C elegans and cancer, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Those who were exposed to metformin during fetal life had a larger upper arm circumference and bigger subscapular skin folds and biceps, suggesting a better fat distribution than children exposed to insulin(251).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Safety of metformin during pregnancy
What the sources say
- Not checked yetcites [251] Rowan, 2011, Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age, Diabetes Care source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Metformin has a molecular weight of 129 dalton, and it crosses the placenta in direct diffusion without affecting the facilitated transfer of glucose(242).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Safety of metformin during pregnancy
What the sources say
- Not checked yetcites [242] Nanovskaya, 2006, Transfer of metformin across the dually perfused human placental lobule, Am J Obstet Gynecol source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In a meta-analysis(255), metformin-treated diabetic patients had a 31% reduction in the incidence of cancer and a 34% reduction in cancer mortality after adjusting for body mass index(255).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > A role for metformin in cancer and aging
What the sources say
- Not checked yetcites [255] Gandini, 2014, Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders, Cancer Prev Res source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, there were no differences in fat measurements, total fat mass, and percentage of body fat(251).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Safety of metformin during pregnancy
What the sources say
- Not checked yetcites [251] Rowan, 2011, Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age, Diabetes Care source
plain- Asserted: passes — The authors put it forward as true.
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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, long known to be an herbal medicine, has evolved from its use as a popular treatment for diabetes into a drug with a significantly wider array of beneficial effects ranging from cancer treatment to extending longevity, as well as, in our field, gestational hypertension and preeclampsia in obese women.”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“By preventing access to the nucleus, RagC becomes incapable of stimulating mTORC1 and, therefore, stimulates cellular growth (Figure 12)(278).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > A role for metformin in cancer and aging
What the sources say
- Not checked yetcites [278] Wu, 2016, An ancient, unified mechanism for metformin growth inhibition in C elegans and cancer, Cell source
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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It may state two separate claims as one.
The paper relies on this without support.
Findings on metformin's lifespan extension in worms and mice are applicable to humans.
“Metformin, long known to be an herbal medicine, has evolved from its use as a popular treatment for diabetes into a drug with a significantly wider array of beneficial effects ranging from cancer treatment to extending longevity, as well as, in our field, gestational hypertension and preeclampsia in obese women.”
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
“We now know there are extra-hepatic sites of action of metformin with the gut being a major contributor to its clinical benefits as an anti-hyperglycemic drug via modulating glucagon-like peptide 1 (GLP-1) levels by a duodenal AMPK-mediated pathway, as well as effects resulting from modulating the microbiota (25–29).”
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 [27]
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, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Two trials from the UK report conflicting results of treating obese, non-diabetic, pregnant women with metformin
“The finding that metformin decreased the frequency of preeclampsia was consistent with the findings reported in a meta-analysis by Gui et al.(75) and Feng and Yang(76).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > Metformin: from the Pharaohs to the Present > Important results from the meta-analyses: metformin reduces the frequency of gestational hypertension in gestational diabetes
“however, metformin did not change the frequency of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) fetuses or of hypoglycemia and preeclampsia(75).”
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, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > A role for metformin in cancer and aging
“By preventing access to the nucleus, RagC becomes incapable of stimulating mTORC1 and, therefore, stimulates cellular growth (Figure 12)(278).”
§ Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity > A role for metformin in cancer and aging
“Biguanides inhibit growth by suppressing mitochondrial respiration, which limits the transit of the complex RagA-RagC GTPase heterodimer through the nuclear pore complex(278).”
Citations
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
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Circulating angiogenic factors and the risk of preeclampsia
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Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
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Metadata
- Authors
- Romero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H., & Grossman, L. I.
- Affiliations
- United States Department of Health and Human Services (US)
- Ben-Gurion University of the Negev (IL)
- Wayne State University (US)
- Seoul National University (KR)
- Corresponding author
- Romero, Roberto
- Erez, Offer
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 217
- Issue
- 3
- Pages
- 282-302
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC6084482
- OpenAlex
- W2625297718
- Semantic Scholar
- 4dc479bc8b2017b127f102653c2604ced2829137
- Cited by
- 253
- References
- 293
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 24 · 2023: 25 · 2022: 34 · 2021: 38 · 2020: 29 · 2019: 30 · 2018: 39 · 2017: 8
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201300006C, ZIAHD002400)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, gestational diabetes mellitus, preeclampsia prevention, prediabetes, polycystic ovary syndrome, macrosomia, large for gestational age, anti-angiogenic factors, soluble fms-like tyrosine kinase-1, soluble endoglin, endothelial dysfunction, mitochondrial function, rapamycin, energy homeostasis, placental transfer, drug safety in pregnancy, chemoprevention, longevity, aging
- MeSH terms
- Female, Humans, Hypoglycemic Agents, Longevity, Maternal-Fetal Exchange, Metformin, Neoplasms, Pre-Eclampsia, Pregnancy, Randomized Controlled Trials as Topic, Diabetes, Gestational, Maternal Nutritional Physiological Phenomena, Fetal Development, TOR Serine-Threonine Kinases
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