Allan S. Brett, MD reviewing Hong J et al. Diabetes Care 2013 May

Metformin was associated with better cardiovascular outcomes.


Observational data have suggested that metformin, compared with sulfonylureas, protects patients with type 2 diabetes against adverse cardiovascular events. In this double-blind trial from China, researchers randomly assigned 304 diabetic patients with documented coronary artery disease to receive either metformin or glipizide for 3 years. At baseline, mean glycosylated hemoglobin (HbA1c) was 7.6%; most patients were taking aspirin and statins. During the study, insulin was added in about 25% of patients in each group. After the formal 3-year randomized intervention, monitoring of patients continued, with average total follow-up of 5 years.

The primary outcome was a broad composite of nonfatal cardiovascular events and death from any cause. Sixty events occurred in 41 glipizide recipients (35%), and 43 events occurred in 39 metformin recipients (25%). In a time-to-event analysis, the primary outcome was less likely with metformin than with glipizide (hazard ratio, 0.54; P=0.026). Fourteen patients in the glipizide group and 7 in the metformin group died. Glycemic control and lipid levels were similar in the two groups. On average, glipizide recipients gained 1 kg, and metformin recipients lost 1 kg. The incidence of hypoglycemia was similar in the two groups.


This randomized trial supports the use of metformin, compared with sulfonylureas, in diabetic patients with coronary disease. Guidelines already recommend metformin as first-line oral monotherapy. For patients who clearly require a second agent to maintain acceptable glycemic control, the lingering question — not addressed here — is which add-on therapy is most favorable from a cardiovascular perspective?


Hong J et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease.Diabetes Care 2013 May; 36:1304. [PubMed® abstract]

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