Clinical Question

Does metformin (Glucophage) affect cardiovascular events in patients with type 2 diabetes mellitus?

Bottom Line

Over five years, treatment with metformin for three years, with other hypoglycemics as needed, reduced the likelihood of death, nonfatal stroke, or the need for vascularization compared with treatment beginning with glipizide (Glucotrol). Cardiovascular events were not individually reduced with metformin compared with glipizide. (Level of Evidence = 1b–)

Synopsis

These authors enrolled patients with type 2 diabetes and coronary artery disease, and followed them for a median of five years. The average age of all 304 patients was 63.3 years; 77% were men. After stopping current treatment (which included insulin in approximately 10% of the group), patients were randomized, with allocation concealment unknown, to receive 30 mg of glipizide daily or 1,500 mg of metformin daily, with additional treatment added as needed, to achieve an average A1C level of 7%. In each group, 25% of patients ended up receiving insulin in addition to the study drug. Using intention-to-treat analysis, the investigators compared the incidence of recurrent cardiovascular events in the two groups, including death, nonfatal stroke, or need for revascularization. After a median follow-up of five years, one or more events occurred in 35% of patients treated with glipizide and in 25% of patients treated with metformin (adjusted hazard ratio = 0.54; P = .026), which translates to a number needed to treat of 9.4 for five years. Death rates were not different between the two groups. This small study reinforces the findings from the long-ago study (Diabetes. 1970;19:747–830) that resulted in U.S. Food and Drug Administration warnings of an increased risk of cardiovascular events with sulfonylurea hypoglycemics.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (any)

Reference: HongJZhangYLaiSet alSPREAD-DIMCAD InvestigatorsEffects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care.2013; 36( 5): 1304– 1311.