Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials
Article first published online: 24 JAN 2011
© 2011 Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism
Volume 13, Issue 3, pages 221–228, March 2011
How to Cite
Lamanna, C., Monami, M., Marchionni, N. and Mannucci, E. (2011), Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes, Obesity and Metabolism, 13: 221–228. doi: 10.1111/j.1463-1326.2010.01349.x
- Issue published online: 24 JAN 2011
- Article first published online: 24 JAN 2011
- Accepted manuscript online: 3 DEC 2010 12:40PM EST
- Date submitted 28 August 2010; date of first decision 28 September 2010; date of final acceptance 20 October 2010
- cardiovascular events;
- type 2 diabetes
Aim: Some studies suggested that metformin could reduce cardiovascular risk to a greater extent than that determined by glucose reduction. Aim of the present meta-analysis is to assess the effects of metformin on the incidence of cardiovascular events and mortality.
Methods: An extensive search of Medline, EMBASE and the Cochrane Library (any date up to 31 October 2009) was performed for all trials containing the word ‘metformin’. Randomized trials with a duration ≥52 weeks were included. A meta-regression analysis was also performed to identify factors associated with cardiovascular morbidity and mortality in metformin-treated patients.
Results: A total of 35 clinical trials were selected including 7171 and 11 301 participants treated with metformin and comparator, respectively, who had 451 and 775 cardiovascular (CV) events, respectively. Overall, metformin was not associated with significant harm or benefit on cardiovascular events (MH-OR 0.94[0.82–1.07], p = 0.34). A significant benefit was observed in trials versus placebo/no therapy (MH-OR 0.79[0.64–0.98], p = 0.031), but not in active-comparator trials (MH-OR 1.03[0.72–1.77], p = 0.89). Meta-regression showed a significant correlation of the effect of metformin on cardiovascular events with trial duration and with minimum and maximum age for inclusion, meaning that the drug appeared to be more beneficial in longer trials enrolling younger patients. It is likely that metformin monotherapy is associated with improved survival (MH-OR: 0.801[0.625–1.024], p = 0.076). However, concomitant use with sulphonylureas was associated with reduced survival (MH-OR: 1.432[1.068–1.918], p = 0.016).
Conclusion: Available evidence seems to exclude any overall harmful effect of metformin on cardiovascular risk, suggesting a possible benefit versus placebo/no treatment. The observed detrimental effect of the combination with sulphonylureas deserves further investigation.