Metformin Superior to Glipizide for Reducing CVD Events in Diabetics With CAD

January 03, 2013

SHANGHAI, China — The use of metformin significantly reduced the risk of cardiovascular events among diabetic patients with coronary artery disease when compared with the sulfonylurea glipizide, according to the results of a randomized clinical trial [1]. Over a median follow-up of five years, treatment with metformin reduced the primary composite end point of death from cardiovascular causes, death from any cause, nonfatal MI, nonfatal stroke, and arterial revascularization by 46% compared with glipizide.

The researchers also performed a second analysis examining only cardiovascular events that occurred after one year of treatment--performed to ensure that the cardiovascular events were not caused by the antidiabetic drugs--and found a significant 52% relative reduction in the risk of cardiovascular events.

Led by Dr Jie Hong (Shanghai Jiao Tong University School of Medicine, China), the study, known as the Study on the Prognosis and Effect of Antidiabetic Drugs on Type 2 Diabetes Mellitus with Coronary Artery Disease (SPREAD-DIMCAD), is published December 10, 2012 in Diabetes Care. The trial included 304 patients with type 2 diabetes and coronary artery disease randomly assigned to glipizide 30 mg or metformin 1.5 mg for three years. Patients had been diagnosed with diabetes for more than five years and with coronary artery disease for three years.

In total, there were 103 primary composite events in 91 patients, including 52 patients in the glipizide arm and 39 patients in the metformin arm. There were 60 clinical events in the glipizide-treated patients, including 14 deaths from all causes (11 deaths from cardiovascular causes and three from sudden death), six MIs, 15 nonfatal strokes, and 25 arterial revascularizations. In the metformin arm, there were 43 clinical events, including seven deaths from all causes (all were cardiovascular deaths), five MIs, 10 nonfatal strokes, and 21 revascularizations. This translated into a relative reduction in risk of 46% (hazard ratio 0.54; 95% CI 0.30–0.90). There was no difference in the mortality rate between the two treatment groups.

Regarding secondary end points, there was no observed difference among patients in terms of new or worsening heart failure, new cardiac arrhythmias, new or worsening angina, or new peripheral vascular events. There was also no significant difference in terms of patients reporting one or more hypoglycemic attacks.

In their paper, Hong et al point out that metformin has been shown to have antiatherogenic properties, such as the ability to reduce markers of inflammation and to reduce vascular adhesion molecules and coagulation parameters. Metformin has also been shown to reduce endothelial dysfunction. "In addition, sulfonylureas are associated with weight gain, whereas metformin is associated with weight loss," write the researchers. "Weight gain may negate the beneficial effects of sulfonylureas on glucose and increase mortality."

They add that statin use among the diabetic patients was significantly lower among those treated with metformin (59.5% vs 73.7% in the glipizide-treated patients; p=0.013), even though there was no significant difference in lipid levels between the treatment arms. "These findings further strengthened the beneficial long-term effects of metformin, which might be associated with the antiatherosclerotic properties beyond glucose lowering," write Hong et al.