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

  1. on behalf of the SPREAD-DIMCAD Investigators*
  1. 1Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  2. 2Johns Hopkins University School of Medicine, Baltimore, Maryland
  3. 3Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  4. 4The Second Xiangya Hospital of Central South University, Changsha, China
  5. 5Shandong Provincial Hospital, Shandong University, Jinan, China
  6. 6Chang Hai Hospital, Second Military Medical University, Shanghai, China
  7. 7The First Affiliated Hospital of Wenzhou Medical College, Zhejiang Province, China
  8. 8Sir Run Run Shao Hospital, Zhejiang Province, China
  9. 9Jiangsu Province Hospital, Jiangsu Province, China
  10. 10Shanghai Ten’s People’s Hospital of Tongji University, Shanghai, China
  11. 11Nanfang Hospital, Guangdong Province, China
  12. 12Nanjin Drum Tower Hospital, Jiangsu Province, China
  1. Corresponding author: Guang Ning, guangning{at}
  1. J.H. and Y.Z. contributed equally to this study.


OBJECTIVE The two major classes of antidiabetic drugs, sulfonylureas and metformin, may differentially affect macrovascular complications and mortality in diabetic patients. We compared the long-term effects of glipizide and metformin on the major cardiovascular events in type 2 diabetic patients who had a history of coronary artery disease (CAD).

RESEARCH DESIGN AND METHODS This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 304 type 2 diabetic patients with CAD, mean age = 63.3 years (range, 36–80 years), were enrolled. Participants were randomly assigned to receive either glipizide (30 mg daily) or metformin (1.5 g daily) for 3 years. The primary end points were times to the composite of recurrent cardiovascular events, including death from a cardiovascular cause, death from any cause, nonfatal myocardial infarction, nonfatal stroke, or arterial revascularization.

RESULTS At the end of study drug administration, both groups achieved a significant decrease in the level of glycated hemoglobin (7.1% in the glipizide group and 7.0% in the metformin group). At a median follow-up of 5.0 years, 91 participants had developed 103 primary end points. Intention-to-treat analysis showed an adjusted hazard ratio (HR) of 0.54 (95% CI 0.30–0.90; P = 0.026) for the composites of cardiovascular events among the patients that received metformin, compared with glipizide. The secondary end points and adverse events were not significantly different between the two groups.

CONCLUSIONS Treatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide. Our results indicated a potential benefit of metformin therapy on cardiovascular outcomes in high-risk patients.


  • * A complete list of the investigators of SPREAD-DIMCAD can be found in the appendix.

  • Received April 16, 2012.
  • Accepted October 4, 2012.

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  1. Diabetes Care
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