Metformin May Be Linked to Lower Risk of Death from Cardiovascular Disease

A meta-analysis of 40 previously published studies conducted by Elizabeth Selvin, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health, and colleagues has found that treatment with the diabetes drug metformin may be associated with a lower risk of death from cardiovascular disease.

The results of their analysis, published in the October 27 issue of Archives of Internal Medicine, led the authors to conclude that “compared with other oral diabetes agents and placebo, metformin was moderately protective and rosiglitazone possibly harmful, but lack of power prohibited firmer conclusions.”

In their introductory remarks, the authors note that even though there is a wide variety of oral diabetes medications available for the treatment of type 2 diabetes mellitus, most trials “examining the efficacy of these different therapies have largely focused on intermediate clinical outcomes such as changes in levels of hemoglobin A1c (HbA1c) or serum lipids and in blood pressure.” Less clear are specific effects of oral diabetes agents on cardiovascular risks.

Accordingly, the authors searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for studies that would enable them to “systematically examine the peer-reviewed literature on the cardiovascular risk associated with oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, and meglitinides) for treating adults with type 2 diabetes.”

The authors’ search criteria included studies of frequently prescribed therapy combinations (including metformin, second-generation sulfonylureas, and thiazolidinediones), but excluded studies that evaluated “combinations of any 3 oral diabetes agents and studies of first-generation sulfonylureas,” on the grounds that physicians prescribed these medications. They also excluded studies that did not report all-cause mortality or cardiovascular morbidity or mortality, as well as studies that were less than three months in duration and/or that enrolled fewer than 40 subjects.

Analysis of data from all included studies demonstrated that, when compared with any other treatment or placebo, metformin was associated with a “statistically significant decrease in cardiovascular mortality.” The authors noted too that “estimates for metformin with cardiovascular morbidity and all-cause mortality were similar but not statistically significant.”

The authors cautioned that their findings should be considered in the context of “the limitations of the published literature on oral diabetes medications,” noting the relatively few published trials that have examined the comparative effectiveness of oral diabetes medications on cardiovascular outcomes. They also pointed out that “there have been few trials of oral diabetes therapies that have lasted longer than 6 months and that reporting of adverse events for cardiovascular disease is poor.”