Effects of Metformin Versus Glipizide on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Coronary Artery Disease

Study Questions:

What is the differential impact of glipizide and metformin among Chinese type 2 diabetic patients with a history of coronary artery disease (CAD) on macrovascular complications and mortality in a clinical trial?


This was a multicenter, randomized, double-blind, placebo-controlled clinical trial (SPREAD-DIMCAD). Participants were randomly assigned to receive either placebo, glipizide (30 mg daily), or metformin (1.5 g daily) for 3 years. The primary endpoints were a composite of recurrent cardiovascular events.


A total of 304 type 2 diabetic patients with CAD (mean age 63.3 years) were enrolled. At the end of study drug administration, both groups achieved a significant decrease in the level of glycosylated hemoglobin to essentially target levels (7.1% in the glipizide group and 7.0% in the metformin group). At the median follow-up of 5 years, the adjusted hazard ratio for the composite of cardiovascular events among those receiving metformin was 0.54 (95% confidence interval, 0.30-0.90; p = 0.026), compared to those receiving glipizide. While the body mass index was significantly lower in the metformin group than in the glipizide group after treatment, these values were minimally elevated to begin with at 25.1 ± 2.9 kg/m2 and 25.2 ± 3.0 kg/m2 in the glipizide and metformin groups, respectively.


Compared with glipizide, 3-year treatment with metformin substantially reduced composite cardiovascular events, even though these antidiabetic drugs were independently successful in establishing glycemic control.


While limited by a sample size and generalizability to other populations, the current findings of a potential benefit of metformin therapy on cardiovascular outcomes in type 2 diabetic patients lend support to contemporary practice patterns to use this as first-line therapy anyway. The implications of weight loss associated with metformin would probably only potentiate the reduction in macrovascular complications associated with metformin therapy in more obese populations.

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Follow-Up Studies, Weight Loss, Diabetes Mellitus, Type 2, Asian Continental Ancestry Group, Hemoglobin A, Glycosylated, Body Mass Index, Metformin, Blood Glucose, Cardiovascular Diseases, Obesity, Hypoglycemic Agents, Diabetes Mellitus

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