Fewer deaths/strokes/revascularizations with metformin than glipizide.

Clinical Question:  Does metformin affect cardiovascular events in patients with type 2 diabetes?

Bottom Line

Over 5 years, treatment with metformin for 3 years, along with other hypoglycemics as needed, reduced the likelihood of death, nonfatal stroke, or the need for vascularization as compared with treatment beginning with glipizide. Cardiovascular events were not individually reduced with metformin as compared with glipizide. (LOE = 1b-)


Hong J, Zhang Y, Lai S, et al, for the SPREAD-DIMCAD Investigators. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care 2013;36(5):1304-1311.

Study design: Random double-blinded controlled study

Funding: Govt

Setting: Outpatient

Allocation: Uncertain


These Chinese authors enrolled patients with type 2 diabetes and coronary artery disease and followed them up for a median of 5 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 either glipizide 30 mg daily or metformin 1500 mg daily, with additional treatment added as needed, to achieve an average glycated hemoglobin level of 7.0%. Twenty-five percent of patients in each group 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 2 groups, including death, nonfatal stroke, or need for revascularization. After a median follow-up of 5 years, one or more events occurred in 35.1% of patients treated with glipizide and 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 5 years. Death rates were not different between the 2 groups. This small study reinforces the findings from the long-ago study (Diabetes 1970;19:747-830) that resulted in FDA warnings of an increased risk of cardiovascular events with sulfonylurea hypoglycemics.

Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA


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