The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index; none of the 16 sources its claims cite is checked for support yet.
Improved endothelial function with metformin in type 2 diabetes mellitus
Open accessAbstract
Objectives This study was designed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus.Background Abnormalities in vascular endothelial function are well recognized among patients with type 2 (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction. The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported.Methods Subjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses to intraarterial administration of endothelium-dependent (acetylcholine), endothelium-independent (sodium nitroprusside) and nitrate-independent (verapamil) vasodilators were measured using forearm plethysmography. Whole-body insulin resistance was assessed on both occasions using the homeostasis model (HOMA-IR).Results Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil-stimulated (p = 0.40) flows. There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012).Conclusions Metformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables. This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus. This has important implications for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In diet-treated type 2 diabetes patients without the clustered metabolic syndrome risk factors, 12 weeks of metformin improved endothelium-dependent forearm blood flow and insulin resistance compared with placebo. Post-treatment insulin resistance was the sole predictor of endothelium-dependent vasodilation, supporting a central role for insulin resistance in endothelial dysfunction.
Key findings
- Metformin significantly improved acetylcholine-stimulated forearm blood flow versus placebo (p = 0.0027 by two-way ANOVA), while no significant treatment effect was seen for sodium nitroprusside (p = 0.27) or verapamil (p = 0.40).
- Metformin produced a 32.5% reduction in HOMA-IR (p = 0.01), with no change in the placebo group; FFA also changed significantly (p = 0.019).
- After treatment, stepwise multivariate analysis found insulin resistance (logHOMA-IR) was the sole predictor of endothelium-dependent blood flow (r = −0.659, adjusted r² = 0.434, p = 0.0012).
- Glucose, HbA1c, weight, blood pressure, and cholesterol did not show significant treatment-attributable changes.
Methods
- Randomized, placebo-controlled study of patients with diet-controlled type 2 diabetes without other major cardiovascular risk factors; participants received metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks, with 44 subjects initially enrolled and 4 withdrawals.
- Forearm strain-gauge plethysmography measured blood flow responses to intraarterial acetylcholine (endothelium-dependent), sodium nitroprusside (endothelium-independent), and verapamil (nitrate-independent); whole-body insulin resistance was assessed by HOMA-IR.
- Main analyses used two-way repeated-measures ANOVA, ANCOVA, linear regression, and forward stepwise regression.
Limitations
- The paper states that oxidative balance/oxidative stress and LDL particle size were not measured, though these variables affect endothelial function and may be affected by metformin.
- Evident from the text: the study was small, baseline LDL cholesterol was significantly lower in the placebo group, and FFA levels showed a borderline baseline difference favoring placebo.
- Evident from the text: pretreatment sodium nitroprusside responses unexpectedly differed between groups, and the direct correlation between change in insulin resistance and improvement in endothelial response did not reach statistical significance.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
17 Own result · 10 Not checked yet · 10 Own method · 7 Own interpretation · 1 No basis given
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
“There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p ϭ 0.01)”
- Also stated in: § Demographics. · plain
“Metformin produced a significant 32.5% drop in HOMA-IR, whereas no change was seen in the patients receiving placebo.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
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.
- Also stated in: § Demographics. · plain
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
“The inclusion of these variables with the change in BMI and in lipid variables in a multivariate model accounted for Ͼ95% of the variation in the change in endothelial response (p ϭ 0.005).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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.
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
“by stepwise multivariate analysis insulin resistance was the sole predictor of endotheliumdependent blood flow following treatment (r ϭ Ϫ0.659, p ϭ 0.0012).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
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.
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
“After therapy with metformin, univariate ANOVA revealed an effect of logHOMA-IR (p ϭ 0.06) and of body mass index (BMI) (p ϭ 0.007) on endothelial responses.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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.
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
“Of note, no relationship with LDL cholesterol, ambient glucose, Hb A1c or FFA level was evident.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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 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
“whereas no significant effect was seen on nitroprusside-stimulated (p ϭ 0.27) or verapamil-stimulated (p ϭ 0.40) flows.”
- Also stated in: § Blood flow responses. · plain
“across all doses there was no statistically significant treatment effect relative to placebo (p ϭ 0.27).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
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.
- Also stated in: § Blood flow responses. · plain
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
“Metformin treatment resulted in statistically significant improvements only in HOMA-IR and FFA levels compared to placebo”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
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.
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
“Verapamil-induced, nitrateindependent flows were not different between groups either before or after treatment (p ϭ 0.40, Fig. 3).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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 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
“In the present study, the direct correlation between the change in IR and the improvement in endothelial response did not achieve statistical significance”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
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.
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
“but the combination of changes in IR, lipids, FFAs and BMI was able to account for the vast majority of the change in endothelial response.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
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.
- The quote only partly states this claim. 2
- It may state two separate claims as one. 14
- Probably not a substantial claim. 13
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
“Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p ϭ 0.0027 by 2-way analysis of variance)”
- Also stated in: § DISCUSSION · plain
“In patients with IR and type 2 DM, three months of treatment with metformin improved endotheliumdependent vascular responses, whereas vascular responses of patients treated with placebo remained unchanged.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
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.
The quote only partly states this claim.
- Also stated in: § DISCUSSION · plain
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
“without significant changes in body mass index, blood pressure or cholesterol levels.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
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.
It may state two separate claims as one.
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
“Treatment effects on glucose (0.5 mmol/l reduction) and weight (1.5 kg) were small and did not achieve statistical significance.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Demographics.
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.
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
“Although the change in response at peak dose was statistically significant for metformin-treated subjects compared with their baseline (p ϭ 0.01), across all doses there was no statistically significant treatment effect relative to placebo (p ϭ 0.27).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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.
It may state two separate claims as one.
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
“At baseline, univariate ANOVA revealed no effect of any metabolic or anthropomorphic parameters on endothelial responses, and similarly by ANCOVA there were no significant interactions of these effects on baseline responses.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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.
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
“Following therapy, linear regression analyses revealed dependencies of endothelium-dependent responses following therapy on BMI (r ϭ Ϫ0.43, p ϭ 0.007), logHOMA-IR (r ϭ Ϫ0.486, p ϭ 0.017) (Fig. 4) and high density lipoprotein cholesterol (r ϭ 0.34, p ϭ 0.036).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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.
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
“Baseline endothelium-independent nitrate responses were unexpectedly higher in the group who received placebo, but at the end of treatment this difference was abolished (Fig. 2).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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
“Abnormalities in endothelium-dependent vascular responses, perhaps the earliest demonstrable alteration in vascular health, have been found among patients with type 2 DM (2,3).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
What the sources say
- Not checked yetcites [2] McVeigh, 1992, Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus, Diabetologia source
- Not checked yetcites [3] Williams, 1996, Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus, J Am Coll Cardiol 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.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Medication compliance was Ͼ95% by pill count.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Demographics.
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This trial was designed and performed in accordance with the principles of the Declaration of Helsinki and was approved by our University's Ethical Review Board.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Patients.
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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not undertake any measure of oxidative balance or oxidative stress, nor was LDL particle size measured.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Study limitations.
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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Written informed consent was obtained after the purpose, nature and potential risks of the interventions were explained to the subjects.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Patients.
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
“In fact, metformin has recently been reported to have antioxidant effects (34) in addition to the known favorable effects on circulating lipids (10) and FFAs (35).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
What the sources say
- Not checked yetcites [34] Faure, 1999, An insulin sensitizer improves the free radical defence system potential and insulin sensitivity in high fructose-fed rats, Diabetes source
- Not checked yetcites [10] Bailey, 1996, Metformin, N Engl J Med source
- Not checked yetcites [35] Abbasi, 1998, Further evidence for a central role of adipose tissue in the antihyperglycemic effect of metformin, Diabetes Care 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“End point measures including blood flow data analyses were blinded to patient name, treatment assignment and treatment timing.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Patients.
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
“Also, in ex-vivo preparations of vascular smooth muscle, a direct vasodilating action of metformin has been reported, possibly due to altered calcium handling (35,37,38).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
What the sources say
- Not checked yetcites [35] Abbasi, 1998, Further evidence for a central role of adipose tissue in the antihyperglycemic effect of metformin, Diabetes Care source
- Not checked yetcites [37] Bhalla, 1996, Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat, Am J Hypertens source
- Not checked yetcites [38] Dominguez, 1996, Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle, Endocrinology 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
“Insulin resistance is felt to be central to the pathogenesis of the metabolic syndrome (Syndrome X), a clustering of traditional cardiovascular risk factors in patients with type 2 DM (8).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
What the sources say
- Not checked yetcites [8] Reaven, 1988, Role of insulin resistance in human disease, Diabetes source
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.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Subjects assigned to metformin and placebo were well matched for degree of obesity and level of glycemic control, and both the fasting insulin level and the calculated index of IR indicated equivalent degrees of IR.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Demographics.
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.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Four subjects withdrew from the study before the second set of measurements, two of whom had been assigned to receive metformin therapy.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Demographics.
plainn = 4- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Flow data analysis was performed at a later date by investigators blind to patient name, study day and treatment assignment.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Vascular responses.
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The level of low density lipoprotein (LDL) cholesterol was significantly lower in the group who received placebo.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Demographics.
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.
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
“Again, ANCOVA revealed no interactions, suggesting that the chance imbalances between groups, particularly with regard to LDL cholesterol, did not influence the results.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Blood flow responses.
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.
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 treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables.”
- Also stated in: § Conclusions. · plain
“In our group of patients with type 2 DM and IR but without other metabolic abnormalities, we found that treatment with metformin resulted in improved IR and improved endothelial function.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > RESULTS
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. The quote only partly states this claim.
- Also stated in: § Conclusions. · plain
In the paper
“Despite a clear improvement in insulin sensitivity with treatment, no improvement in insulin-mediated or agonist-stimulated vasodilation was seen.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
What the sources say
- Not checked yetcites [32] Tack, 1998, Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone, Diabetologia source
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: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A direct metformin effect in vascular endothelial cells is also possible, and supported by recent findings in insulin-resistant rats (36).”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
What the sources say
- Not checked yetcites [36] Katakam, 2000, Metformin improves vascular function in insulin-resistant rats, Hypertension source
hedgeddirect- 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.
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
“However, an important effect of IR per se on endothelial function is suggested by the fact that a relationship was not evident at baseline but was brought out by metformin therapy, which concurrently improved insulin sensitivity and endothelial function.”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > DISCUSSION
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.
The paper relies on this without support.
The effects of altering insulin resistance with metformin on endothelial function in humans have not been previously reported.
“The effects of altering IR with metformin on endothelial function in humans have not been previously reported.”
“The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported.”
The paper relies on this without support.
No evidence links alterations in antioxidant, lipid, or FFA parameters with improvements in vascular function separate from improvements in insulin resistance.
“However, no evidence links alterations in these parameters with improvements in vas-cular function separate from improvements in IR, and therefore the hypothesis of the central role of IR remains plausible.”
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
“Mather et al. reported that compared to placebo, metformin improved endothelium-dependent, but not endothelium-independent vasodilation thus highlighting the primary dysfunction in blood flow was not the vascular smooth muscle response but was secondary to endothelial dysfunction (106).”
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 [106]
In the citing paper
“Based on critical reviews of the literature, the answer appears to be “yes”, although the clinical data could be interpreted as secondary to metformin’s actions to enhance insulin sensitivity and lower blood glucose levels (34, 106, 173).”
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 [106]
In the citing 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].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [89]
In the citing 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].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [89]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
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
“| Parameter | (n ؍ 15) | (n ؍ 28) | | Age (yrs) | 54.8 (2.6) | 50.7 (1.8) | | Gender (M/F) | 11/4 | 15/14 |”
§ Endothelial Function Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus > Conclusions.
Reported 28 · recomputed 29
Citations
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., Palensky, J., & Wittes, J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909023411001 · Cited by 9,214
Katz, A., Nambi, S. S., Mather, K., Baron, A. D., Follmann, D. A., Sullivan, G., & Quon, M. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6661 · Cited by 3,931
Self-citationBonora, E., Targher, G., Alberiche, M., Bonadonna, R. C., Saggiani, F., Zenere, M. B., Monauni, T., & Muggeo, M. (2000) · Diabetes Care · doi:10.2337/diacare.23.1.57 · Cited by 2,456
Role of oxidative stress in diabetic complications: a new perspective on an old paradigm.
Baynes, J. W., & Thorpe, S. R. (1999) · Diabetes · doi:10.2337/diabetes.48.1.1 · Cited by 2,441
Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726
Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118709 · Cited by 1,687
Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus
Williams, S. B., Cusco, J. A., Roddy, M.-A., Johnstone, M. T., & Creager, M. A. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00522-6 · Cited by 1,014
McVeigh, G. E., Brennan, G. M., Johnston, G. D., McDermott, B. J., McGrath, L. T., Henry, W. R., Andrews, J. W., & Hayes, J. R. (1992) · Diabetologia · doi:10.1007/bf00429099 · Cited by 916
Research works printed but not linked: 1
- Paradisi, 1999, Troglitazone therapy improves endothelial function in women with polycystic ovary syndrome, Diabetes, 48, A129
Cited by
Sorted by citations
Items 301–400 of 509
Yener, S., Çömlekçi, A., Akıncı, B., Akan, P., Demir, T., Bayraktar, F., & Yeşil, S. (2008) · HORMONES · doi:10.14310/horm.2002.1111039 · Cited by 18
Metformin prevents vascular prostanoid release alterations induced by a high‐fat diet in rats
Lee, H. J., Cantú, S. M., Donoso, A. S., Choi, M. R., Peredo, H. A., & Puyó, A. M. (2017) · Autonomic and Autacoid Pharmacology · doi:10.1111/aap.12057 · Cited by 18
Reboussin, D. M., Goff, D. C., Lipkin, E. W., Herrington, D. M., Summerson, J. H., Steffes, M. W., Crouse, R. J., Jovanovic, L. G., Feinglos, M. N., Probstfield, J. L., et al. (2004) · Diabetic Medicine · doi:10.1111/j.1464-5491.2004.01289.x · Cited by 18
Do effects on blood pressure contribute to improved clinical outcomes with metformin?
Schäfers, R. F. (2003) · Diabetes & Metabolism · doi:10.1016/s1262-3636(03)72789-x · Cited by 18
Metformina para la diabetes mellitus tipo 2. Revisión sistemática y metaanálisis
Sáenz Calvo, A., Fernández Esteban, I., Mataix Sanjuán, A., Ausejo Segura, M., Roqué, M., & Moher, D. (2005) · Atención Primaria · doi:10.1157/13078602 · Cited by 17
Schinzari, F., Tesauro, M., Campia, U., & Cardillo, C. (2020) · Vascular Pharmacology · doi:10.1016/j.vph.2020.106676 · Cited by 17
Hansen, C. S., Lundby-Christiansen, L., Tarnow, L., Gluud, C. N., Hedetoft, C., Thorsteinsson, B., Hemmingsen, B., Wiinberg, N., Sneppen, S. B., Lund, S. S., et al. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01131-3 · Cited by 17
Vascular reactivity in diabetes mellitus
Chaudhuri, A. (2002) · Current Diabetes Reports · doi:10.1007/s11892-002-0018-1 · Cited by 17
Hollenberg, M. D., & Epstein, M. (2022) · Kidney International Supplements · doi:10.1016/j.kisu.2021.12.001 · Cited by 16
Liu, X., Zhu, H., Peng, Y., Liu, Y., & Shi, X. (2024) · PLoS ONE · doi:10.1371/journal.pone.0299495 · Cited by 16
Reimbursement of metformin for polycystic ovary syndrome
Milewicz, A. (2013) · Endokrynologia Polska · doi:10.5603/ep.2013.0025 · Cited by 18
Insulin Sensitization Therapy and the Heart
Wong, A., Struthers, A. D., Choy, A. M., & Lang, C. C. (2012) · Heart Failure Clinics · doi:10.1016/j.hfc.2012.06.002 · Cited by 17
Metformin: old wine in new bottle--evolving technology and therapy in diabetes.
Joshi, S. (2005) · PubMed · Cited by 15
Li, W., Du, X.-L., Qian, A., Hu, N., Kong, L., Wei, S., Li, C., & Li, X. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.08.091 · Cited by 15
Sinha, P. K., Santr, G., De, D., Sah, A., Kk, B., Bhattachary, P., & Ghosh, P. (2012) · PubMed · Cited by 15
Kang, L., Yi, J., Lau, C., He, L., Chen, Q., Xu, S., Li, J., Xia, Y. Y., Zhang, Y., Huang, Y., et al. (2023) · Antioxidants · doi:10.3390/antiox12091681 · Cited by 14
Huang, L.-Y. M., Yen, I., Tsai, W.-C., Ahmetaj‐Shala, B., Chang, T., Tsai, C., & Lee, S. (2017) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x17500665 · Cited by 14
Poitras, V. J., Bentley, R. F., Hopkins-Rosseel, D. H., LaHaye, S. A., & Tschakovsky, M. E. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00758.2014 · Cited by 14
Extended-Release Metformin Hydrochloride
Wagstaff, A. J., & Figgitt, D. P. (2004) · Treatments in Endocrinology · doi:10.2165/00024677-200403050-00008 · Cited by 14
Potential Cardiovascular Benefits of Insulin Sensitizers
Kunhiraman, B., Jawa, A., & Fonseca, V. A. (2005) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2004.11.005 · Cited by 14
Jadhav, S. T., Petrie, J. R., Ferrell, W., Cobbe, S., & Sattar, N. A. (2004) · Heart · doi:10.1136/hrt.2004.035170 · Cited by 14
Novel therapeutic and diagnostic approaches for preeclampsia
Vatish, M., Powys, V. R., & Cerdeira, A. S. (2023) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000870 · Cited by 13
Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness
Driessen, J. H. M., de Vries, F., van Onzenoort, H. A. W., Schram, M. T., Kallen, C., Reesink, K. D., Sep, S. J. S., Stehouwer, C. D. A., Schaper, N. C., Kroon, A. A., et al. (2019) · Journal of Hypertension · doi:10.1097/hjh.0000000000001892 · Cited by 13
Skov, V., Cangemi, C., Gram, J., Christensen, M. M. H., Grodum, E., Sørensen, D., Argraves, W. S., Henriksen, J. E., & Rasmussen, L. M. (2013) · Diabetes Care · doi:10.2337/dc13-1022 · Cited by 13
Endothelial cell dysfunction in type I and II diabetes: The cellular basis for dysfunction
Pannirselvam, M., Anderson, T. J., & Triggle, C. R. (2003) · Drug Development Research · doi:10.1002/ddr.10127 · Cited by 13
Self-citationThe metabolic syndrome: A vascular perspective
Tamsma, J. T., Jazet, I. M., Beishuizen, E. D., Fogteloo, A. J., Meinders, A. E., & Huisman, M. V. (2005) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2005.01.011 · Cited by 13
Metformin and blood pressure lowering
Thomopoulos, C., Katsimagklis, G., & Makris, T. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000001146 · Cited by 13
Vascular adenosine monophosphate‐activated protein kinase: Enhancer, brake or both?
Chen, H., Vanhoutte, P. M., & Leung, S. W. S. (2019) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13357 · Cited by 14
Insulin Action and Endothelial Function
Mather, K. J., Baron, A., & Quon, M. J. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-116-5_7 · Cited by 12
Self-citationIrving, B. A., & Spielmann, G. (2016) · Diabetes · doi:10.2337/dbi16-0050 · Cited by 12
A Systematic Approach to Managing Hypertension and the Metabolic Syndrome in Primary Care
Bestermann, W. H., Lackland, D. T., Riehle, J. E., & Egan, B. M. (2004) · Southern Medical Journal · doi:10.1097/01.smj.0000129923.83896.cc · Cited by 12
Zhang, T.-X., Xu, J., Peng, F., Chai, D., & Lin, J. (2012) · Blood Pressure · doi:10.3109/08037051.2012.732761 · Cited by 11
Valderrama, I. H., Echeverry, S. M., Rey, D. P., Rodríguez, I. A., Silva, F. R. M. B., Costa, G. M., Ospina-Giraldo, L. F., & Aragón, D. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122758 · Cited by 11
Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights
Sarkar, A., Fanous, K., Marei, I., Ding, H., Ladjimi, M. M., MacDonald, R. S., Hollenberg, M. D., Anderson, T. J., Hill, M. A., & Triggle, C. R. (2024) · Vascular Health and Risk Management · doi:10.2147/vhrm.s391808 · Cited by 11
Self-citationSuzuki, K., Watanabe, K., Suzuki, T., Ouchi, M., Futami‐Suda, S., Igari, Y., Nakano, H., & Oba, K. (2012) · Journal of Diabetes Mellitus · doi:10.4236/jdm.2012.23053 · Cited by 11
Mollnau, H., Oelze, M. W., Zinßius, E., Hausding, M., Wu, Z., Knorr, M., Kerahrodi, J. G., Kröller‐Schön, S., Jansen, T., Teutsch, C., et al. (2013) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-013-0842-7 · Cited by 11
The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1β, IL-6 and IL-10 Secretion
Borowska, M., Dworacka, M., Wesołowska, A., Winiarska, H., Krzyżagórska, E., & Dworacki, G. (2016) · Pharmacology · doi:10.1159/000443897 · Cited by 11
Controversies in Treating Diabetes
LeRoith, D., & Vinik, A. I. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-572-5 · Cited by 11
Redox Modulation of Insulin Signaling and Endothelial Function
Christon, R., Drouin, O., & Marette, A. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1062 · Cited by 11
Gomes, M. B., Cailleaux, S., & Tibiriçá, E. V. (2005) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-005-1083-1 · Cited by 11
Özel, H. F., Alpay, Ş., Asker, E., Gültekin, E. S., & Kazdağlı, H. (2025) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2025.109021 · Cited by 10
Gliquidone versus metformin: differential effects on aorta in streptozotocin induced diabetic rats
Tan, Z., Xu, Z., Gui, Q., Wu, W., & Yang, Y. (2014) · Chinese Medical Journal · doi:10.3760/cma.j.issn.0366-6999.20132950 · Cited by 10
Liu, C., Sun, J., Feng, X., Yi, Y., & Han, A. (2014) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000158 · Cited by 10
Microvascular dysfunction: Determinants and treatment, with a focus on hyperglycemia
Houben, A. J. H. M., & Stehouwer, C. D. A. (2020) · Endocrine and Metabolic Science · doi:10.1016/j.endmts.2020.100073 · Cited by 10
Improved endothelial function with metformin in type 2 diabetes mellitus
Chan, N. N. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01630-8 · Cited by 10
Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis
Pan, Y., & Si, J. (2026) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s565805 · Cited by 9
Aljofan, M., & Gaipov, A. (2019) · Electronic Journal of General Medicine · doi:10.29333/ejgm/108679 · Cited by 9
Assessing the evidence: Exploring the effects of exercise on diabetic microcirculation
Lenasi, H., & Klonizakis, M. (2016) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-168022 · Cited by 9
Vidigal, C. B., Novi, D. R. B. S., Moura, K. F., Picinin, R., Montagnini, B. G., da Silva, R. D. N. O., da Silva, M. D. V., de Andrade, F. G., Akamine, E. H., Gerardin, D. C. C., et al. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.05.050 · Cited by 9
Impact of currently used anti-diabetic drugs on myoendothelial communication
Ding, H., Ye, K., & Triggle, C. R. (2018) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2018.11.002 · Cited by 9
Strey, C. H., Young, J. M., Collier, M., Florkowski, C. M., Shand, B. I., & Scott, R. S. (2004) · Diabetologia · doi:10.1007/s00125-004-1534-0 · Cited by 9
Ragucci, E., Zonszein, J., & Frishman, W. H. (2003) · Heart Disease · doi:10.1097/01.hdx.0000050411.62103.f5 · Cited by 9
Malin, S. K., Heiston, E. M., Battillo, D. J., Ragland, T. J., Gow, A. J., Shapses, S. A., Shah, A. M., Patrie, J. T., & Barrett, E. J. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf551 · Cited by 8
Gu, S., Hu, X., Shi, L., Zhen, X., Sun, X., Huang, M., Gu, Y., & Dong, H. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11237094 · Cited by 8
Crissey, J. M., Padilla, J., Jenkins, N. T., Martin, J. S., Rector, R. S., Thyfault, J. P., & Laughlin, M. H. (2013) · Microcirculation · doi:10.1111/micc.12078 · Cited by 8
Cardiovascular Effects of Noninsulin, Glucose-Lowering Agents: Need for More Outcomes Data
Joshi, P. H., Kalyani, R. R., Blumenthal, R. S., & Donner, T. W. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.08.030 · Cited by 8
Copper, Zinc and Magnesium in Non-Insulin-Dependent Diabetes Mellitus Treated with Metformin
Daniela, M., Ruxandra, C., Tony, L., & Nechifor, M. (2013) · InTech eBooks · doi:10.5772/48230 · Cited by 8
Targeting the vascular dysfunction: Potential treatments for preeclampsia
Marshall, S. A., Langston‐Cox, A., Parry, L. J., & Wallace, E. M. (2018) · Microcirculation · doi:10.1111/micc.12522 · Cited by 8
Campbell, I. W. (2007) · The British Journal of Diabetes · doi:10.1177/14746514070070051001 · Cited by 8
Nash As Part of the Metabolic (Insulin Resistance) Syndrome
Marchesini, G., & Bugianesi, E. (2004) · Wiley eBooks · doi:10.1002/9780470987438.ch5 · Cited by 8
Pușcașu, C., Zbârcea, C. E., Ungurianu, A., Ștefănescu, E., Chiriță, C., Blebea, N. M., & Negreș, S. (2024) · Pharmaceuticals · doi:10.3390/ph17060783 · Cited by 9
Preventing Cardiovascular Disease in Patients with Diabetes: Use of Aspirin for Primary Prevention
Desai, D., Ahmed, H. M., & Michos, E. D. (2015) · Current Cardiology Reports · doi:10.1007/s11886-015-0566-z · Cited by 7
Jassal, D. S., Neilan, T. G., Picard, M. H., & Wood, M. J. (2007) · Echocardiography · doi:10.1111/j.1540-8175.2007.00455.x · Cited by 7
Psallas, M., & Manes, C. (2012) · Europe PMC (PubMed Central) · Cited by 7
Zhou, L., Cai, X., Yang, W., Han, X., & Ji, L. (2017) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/63025 · Cited by 7
Scientific Review and Clinical Applications
Levinson, W. S. (2002) · JAMA · doi:10.1001/jama.287.3.379 · Cited by 7
Genetic abnormalities of the endothelium
BUTANY, J. W., Verma, S., Leask, R. L., Mohsen, B., & Asa, S. L. (2002) · Microscopy Research and Technique · doi:10.1002/jemt.10240 · Cited by 7
Self-citationThe anti-aging role of metformin, clinical applications to pursue the longevity road
Pozzi, M., Susini, P., Seclì, D. D., Diluiso, G., Mendes, V. M., Grimaldi, L., & Schettino, M. (2024) · European Journal of Plastic Surgery · doi:10.1007/s00238-024-02211-3 · Cited by 6
Transcriptomic effects of metformin in skeletal muscle arteries of obese insulin-resistant rats
Padilla, J., Thorne, P. K., Martin, J. S., Rector, R. S., Akter, S., Davis, J. W., Laughlin, M. H., & Jenkins, N. T. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370216689825 · Cited by 6
Erectile dysfunction as a possible important side effect of metformin: A case report
Ngu, M. H., Zakaria, R., Zulkifli, M. M., & Rahman, R. A. (2023) · Malaysian Family Physician · doi:10.51866/cr.282 · Cited by 6
Drug treatments to restore vascular function and diabesity
Cardillo, C. (2012) · Annales Pharmaceutiques Françaises · doi:10.1016/j.pharma.2012.09.001 · Cited by 6
Lambadiari, V., Dimitriadis, G., & Kadoglou, N. P. E. (2018) · Heart Failure Reviews · doi:10.1007/s10741-018-9690-3 · Cited by 6
Κender, Ζ., Groener, J. B., Reismann, P., & Kopf, S. (2019) · Orvosi Hetilap · doi:10.1556/650.2019.31547 · Cited by 6
Widlansky, M. E., & Malik, M. A. (2015) · Springer eBooks · doi:10.1007/978-3-642-37078-6_8 · Cited by 6
Königstein, K., Meier, J., Angst, T., Maurer, D. J., Kröpfl, J. M., Carrard, J., Infanger, D., Baumann, S., Bischofsberger, I., Harder, M., et al. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02905-1 · Cited by 6
Metformin monotherapy for type 2 diabetes mellitus
Sáenz, A., Fernandez-Esteban, I., Mataix, A. L., Segura, M. A., Figuls, M. R. I., & Moher, D. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002966.pub4 · Cited by 6
RetractedZARICH, S. W. (2005) · Cardiology Clinics · doi:10.1016/j.ccl.2004.06.004 · Cited by 6
Masterclass series in peripheral arterial disease
Collinson, D. J., Rea, R., & Donnelly, R. (2004) · Vascular Medicine · doi:10.1191/1358863x04vm550xx · Cited by 6
Tengbom, J., Kontidou, E., Collado, A., Yang, J., Alvarsson, M., Brinck, J. W., Rössner, S. M., Zhou, Z., Pernow, J., & Mahdi, A. (2024) · Clinical Science · doi:10.1042/cs20240447 · Cited by 5
Glucose Supply and Insulin Demand Dynamics of Antidiabetic Agents
Monte, S. V., Schentag, J. J., Adelman, M. H., & Paladino, J. A. (2010) · Journal of Diabetes Science and Technology · doi:10.1177/193229681000400219 · Cited by 5
Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling
Fan, L., Meng, C., Wang, X., Wang, Y., Li, Y., Lv, S., & Zhang, J. (2023) · Clinics · doi:10.1016/j.clinsp.2023.100263 · Cited by 4
Efectos cardiovasculares y seguridad de los fármacos hipoglucemiantes: situación actual
Masmiquel, L. (2013) · Medicina de Familia SEMERGEN · doi:10.1016/j.semerg.2012.12.001 · Cited by 4
Sharrack, N., Knott, K. D., Gulsin, G. S., Kotecha, T., Brown, L., Yeo, J. L., Porcari, A., Adam, R. D., Thirunavukarasu, S., Chowdhary, A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-77280-2 · Cited by 5
Lipid Effects and Cardiovascular Disease Risk Associated with Glucose-Lowering Medications
Stähli, B. E., Gebhard, C., & Tardif, J. (2015) · Current Cardiology Reports · doi:10.1007/s11886-015-0608-6 · Cited by 4
Diabetes and Pancreatic Cancer: A Bidirectional Relationship Perspective
Gupta, M. K., Sarojamma, V., & Vadde, R. (2019) · Springer eBooks · doi:10.1007/978-981-32-9393-9_3 · Cited by 4
Poitras, V. J., Bentley, R. F., Hopkins-Rosseel, D. H., LaHaye, S. A., & Tschakovsky, M. E. (2015) · Physiological Reports · doi:10.14814/phy2.12487 · Cited by 4
Markos, F., Shortt, C. M., Edge, D., Ruane-O’Hora, T., & Noble, M. I. M. (2014) · Physiological Research · doi:10.33549/physiolres.932736 · Cited by 4
Endothelial Dysfunction and Metabolic Syndrome
Lee, S. K., Khambhati, J., Bhargava, A., Engels, M. C., Sandesara, P. B., & Quyyumi, A. A. (2017) · Hypertension Journal · doi:10.5005/jp-journals-10043-0075 · Cited by 4
Potential vascular α1-adrenoceptor blocking properties of metformin in rat aorta and tail artery
Álvarez-Cámara, J. F., Ramirez-Rosas, M. B., Medina-Terol, G. J., Silva‐Velasco, D. L., Velazco-Paz, A., Sánchez‐López, A., Guzmán‐Priego, C. G., Osuna‐Martínez, U., & Centurión, D. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172498 · Cited by 4
Bailey, C. J. (2013) · Springer eBooks · doi:10.1007/978-3-7091-1331-8_8 · Cited by 4
The Evaluation of Cardiac and Peripheral Arterial Disease in Patients with Diabetes Mellitus
Shen, R., Wiegers, S. E., & Glaser, R. (2007) · Endocrine Research · doi:10.1080/07435800701743869 · Cited by 4
Alexánderson, E., García, A. M., Ochoa-López, J. M., Calleja, R., Sierra-Fernández, C., Iñarra-Talboy, F., Meave‐González, A., Alexánderson-Rosas, G., & González‐Canudas, J. (2009) · PubMed · Cited by 4
Oral Agents for Type-2 Diabetes
Codario, R. A. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-441-8_6 · Cited by 4
Glycemic Control in the Metabolic Syndrome and Implications in Preventing Cardiovascular Disease
Gerich, J. E. (2006) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2006.4.315 · Cited by 4
Abbink, E. J., Pickkers, P., Rosendaal, A. J. V., Lutterman, J. A., Tack, C. J., Rüssel, F. G. M., & Smits, P. (2002) · Clinical Science · doi:10.1042/cs1020307 · Cited by 4
Should all diabetic patients receive statins?
Garcia, P. J., & Spellman, C. (2006) · Current Atherosclerosis Reports · doi:10.1007/s11883-006-0059-z · Cited by 4
Cohen, R. A. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000137187.16206.79 · Cited by 4
Comparison of Rosiglitazone and Metformin for Treating HIV Lipodystrophy: A Randomized Trial
van Wijk, J. P. H., de Koning, E. J. P., Cabezas, M. C., op't Roodt, J., Joven, J., Rabelink, T. J., & Hoepelman, A. I. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-143-5-200509060-00009 · Cited by 3
Kobayashi, Y., Iwadare, T., Kobayashi, H., Kimura, T., Ozawa, Y., Kodama, R., Kurozumi, M., Yamazaki, Y., Yamashita, Y., & Umemura, T. (2024) · Clinical Journal of Gastroenterology · doi:10.1007/s12328-024-02074-y · Cited by 3
Han, Y., Lee, K.-Y., Seo, I., & Jung, D. J. (2025) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2025.100663 · Cited by 3
Metadata
- Authors
- Mather, K. J., Verma, S., & Anderson, T. J.
- Affiliations
- Indiana University Indianapolis (US)
- University of Toronto (CA)
- University of Calgary (CA)
- Corresponding author
- Anderson, Todd J
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 37
- Issue
- 5
- Pages
- 1344-1350
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2114391822
- Cited by
- 513
- References
- 47
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 15 · 2023: 10 · 2022: 15 · 2021: 17 · 2020: 19 · 2019: 18 · 2018: 18 · 2017: 27 · 2016: 13 · 2015: 23 · 2014: 20 · 2013: 25 · 2012: 25
- FWCI
- 17.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Alberta Heritage Foundation for Medical Research
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- metformin, endothelial dysfunction, type 2 diabetes, insulin resistance, acetylcholine-induced vasodilation, forearm blood flow, HOMA-IR, insulin-sensitizing drugs, vascular disease
- MeSH terms
- Blood Flow Velocity, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Endothelium, Vascular, Female, Forearm, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Metformin, Middle Aged, Plethysmography, Vasodilation
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).
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 ›
Are you an author, or do you see a problem with this page? Request a review
