Is Metformin Cardioprotective?

Sasali, Afshin; Leahy, Jack L.

doi:10.2337/diacare.26.1.243

Cited by 15 publications

(11 citation statements)

References 18 publications

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“…All-cause mortality of 28% and cardiovascular mortality of 12% over a seven-year follow-up are comparable with 24% and 11% over 5 years in the Canadian study, and 3% per year among middle-aged Finnish men [16]. This is consistent with the theory that it may be metformin that is cardioprotective [15] (rather than sulfonylureas being cardiotoxic). The absolute risk of mortality is surprisingly low in the metformin cohort (8% over 7 years), and the proportion of cardiovascular deaths is less; thus, our study does provide some supporting evidence for this theory.…”

Section: Discussionsupporting

confidence: 80%

“…It has been argued [15] that the results of the Canadian study [1] might support a cardioprotective effect of metformin rather than an increased cardiovascular risk among users of sulfonylureas, possibly derived from unrecognised differences between therapy groups (there was very little clinical information available for patients [15]). It is therefore important to note that the risks associated with sulfonylureas in our study are in line with what would be expected in a diabetic population, despite being higher than those for the metformin cohort.…”

Section: Discussionmentioning

confidence: 99%

“…However, while it is possible that increased risks in the sulfonylureas monotherapy cohort and combination cohort are due to residual confounding or other unknown differences at baseline, the consistently higher risks that we have identified, with results that are similar to previous studies [1], suggest that this issue does warrant further investigation. But, as Sasali and Leahy argue [15], we are not yet in a position to advocate cautious prescribing of sulfonylureas to patients at high cardiovascular risk until further corroborating evidence is available.…”

Section: Discussionmentioning

confidence: 99%

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Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

et al. 2006

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Aims/hypothesis: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. Subjects and methods: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. Results: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA 1c , smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. Conclusions/interpretation: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

et al. 2006

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“…Evans et al suggest that these results support the hypothesis that metformin is cardioprotective, as did Sasali and Leahy [4] in an editorial accompanying our original paper. We question this conclusion, as it remains difficult to fully discern the causal relationship from this series of observational studies.…”

supporting

confidence: 68%

Comment on: Evans JM, Ogston SA, Emslie-Smith A, Morris A (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

et al. 2006

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“…It is known to be an insulin sensitizer and has a low potential to produce adverse effects especially in patients with underlying cardiovascular disease. 6 Several studies have shown that metformin improves vascular functions which reduces cardiovascular events and mortality as a consequence. 7 The mechanism by which metformin attenuates cardiovascular risks in diabetes is not related to its antidiabetic property but rather due to its ability to activate AMPK 2 .…”

Section: Introductionmentioning

confidence: 99%

Effect of metformin on ECG, HR and BP of rats administered with cardiotoxic agent doxorubicin

Emeka

AlAhmed

2017

Int J Basic Clin Pharmacol

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Background: Cardiovascular complications during drug therapy is worrisome and has been known to increase morbidity and mortality. The aim of this study was to investigate the effect of metformin on BP, HR, and ECG, after subacute administration of doxorubicin in rats.Methods: Laboratory acclimatised animals were divided into 4 experimental groups consisting of group I as the control, given 0.5ml normal saline. Group II, received 3mg/kg doxorubicin on alternate days, while group III was given 300mg/kg metformin. The last group of animals were treated with 300mg/kg metformin, 30 min later, the animals were injected doxorubicin ip. The treatment lasted for 15 days thereafter, ECG, HR and BP were measured with anaesthesia.Results: Result showed that doxorubicin induced ECG changes in terms of increased PR and QT intervals significantly. Whereas, QRS and RR intervals were at same time significantly decreased. Metformin was observed to significantly attenuate these changes. In addition, metformin restored decreases in HR that was caused by doxorubicin in a significant fashion. However, metformin alone produced a decrease in HR compared with control. The observed reduced SBP and DBP produced by doxorubicin were also alleviated by the administration of metformin. There were increases in BP parameters measured in normotensive rats with metformin alone.Conclusions: In conclusion, metformin was found to attenuate doxorubicin-induced alteration in ECG pattern and restored the mechanical and physiological functions of the rat heart. Our data further suggests monitoring of CVS changes such as ECG particularly with drugs known to cause myocardial injury.

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Is Metformin Cardioprotective?

Cited by 15 publications

References 18 publications

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

Comment on: Evans JM, Ogston SA, Emslie-Smith A, Morris A (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

Effect of metformin on ECG, HR and BP of rats administered with cardiotoxic agent doxorubicin

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