Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease

Jie Hong, Yifei Zhang, Shenghan Lai, Ankang Lv, Qing Su, Yan Dong, Zhiguang Zhou, Weili Tang, Jiajun Zhao, Lianqun Cui, Dajin Zou, Dawang Wang, Hong Li, Chao Liu, Guoting Wu, Jie Shen, Dalong Zhu, Weiqing Wang, Weifeng Shen, Guang Ning, SPREAD-DIMCAD Investigators, Guang Ning, Jie Hong, Yifei Zhang, Weiqing Wang, Minghui Gui, Ying Chen, Zhenni Chi, Qun Yan, Ying Zhai, Weifeng Shen, Ankang Lv, Ruiyan Zhang, Jialin Yang, Yu Zhang, Xiaofang Fan, Min Hang, Dadong Zhang, Qing Su, Yan Dong, Huili Xing, Zhiguang Zhou, Xing Li, Weili Tang, Jiajun Zhao, Qingbo Guan, Xu Zhang, Lianqun Cui, Liming Chen, Dajin Zou, Juan Li, Yue Chen, Dawang Wang, Feixia Shen, Wenjun Wu, Hong Li, Jiaqiang Zhou, Chao Liu, Tao Yang, Bei Shen, Guoting Wu, Shen Qu, Chunjun Sheng, Xiaoyun Cheng, Jie Shen, Yaoming Xue, Min Wang, Xiangrong Luo, Dalong Zhu, Shanmei Shen, Shenghua Yao, Xiuhua Yu, Huigen Jin, Jia Shi, Bo Feng, Yafang Ni, Shengli Yan, Yangang Wang, Xingji Gong, Jie Hong, Yifei Zhang, Shenghan Lai, Ankang Lv, Qing Su, Yan Dong, Zhiguang Zhou, Weili Tang, Jiajun Zhao, Lianqun Cui, Dajin Zou, Dawang Wang, Hong Li, Chao Liu, Guoting Wu, Jie Shen, Dalong Zhu, Weiqing Wang, Weifeng Shen, Guang Ning, SPREAD-DIMCAD Investigators, Guang Ning, Jie Hong, Yifei Zhang, Weiqing Wang, Minghui Gui, Ying Chen, Zhenni Chi, Qun Yan, Ying Zhai, Weifeng Shen, Ankang Lv, Ruiyan Zhang, Jialin Yang, Yu Zhang, Xiaofang Fan, Min Hang, Dadong Zhang, Qing Su, Yan Dong, Huili Xing, Zhiguang Zhou, Xing Li, Weili Tang, Jiajun Zhao, Qingbo Guan, Xu Zhang, Lianqun Cui, Liming Chen, Dajin Zou, Juan Li, Yue Chen, Dawang Wang, Feixia Shen, Wenjun Wu, Hong Li, Jiaqiang Zhou, Chao Liu, Tao Yang, Bei Shen, Guoting Wu, Shen Qu, Chunjun Sheng, Xiaoyun Cheng, Jie Shen, Yaoming Xue, Min Wang, Xiangrong Luo, Dalong Zhu, Shanmei Shen, Shenghua Yao, Xiuhua Yu, Huigen Jin, Jia Shi, Bo Feng, Yafang Ni, Shengli Yan, Yangang Wang, Xingji Gong

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00513630.

Figures

Figure 1
Figure 1
SPREAD-DIMCAD trial profile.
Figure 2
Figure 2
Changes of major clinical and biochemical characteristics at baseline and during follow-up in different groups. HbA1c (A), fasting plasma glucose (B), BMI (C), triglycerides (D), total cholesterol (E), LDL cholesterol (F), HDL cholesterol (G), and estimated glomerular filtration rate (eGFR) (H). Data displayed as means ± SD. P value refers to comparison between the groups.

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