Metformin reduced CV events compared with glipizide in patients with type 2 diabetes and CAD

A multicenter randomized controlled trial (RCT) of Chinese patients with type 2 diabetes and coronary artery disease (CAD) found that metformin reduced cardiovascular events more than glipizide at 5 years.

The study was published by Diabetes Care on Dec. 10, 2012. The following commentary by Michael Tanner, MD, FACP, was published in the ACP Journal Club section of the April 16 Annals of Internal Medicine.

In SPREAD-DIMCAD, Hong and colleagues randomized 304 high-risk Chinese patients with CAD and mild type 2 diabetes (mean hemoglobin A1c 7.6%) to metformin or glipizide plus placebo 3 times per day for 3 years, with insulin added as needed. The primary outcome was a composite of death, stroke, MI, or revascularization. Metformin and glipizide both reduced hemoglobin A1c (7.0% and 7.1%, respectively), yet the metformin group had fewer CV events (P=0.026).

In simple hypertension, it matters more that blood pressure is reduced than how it is reduced. The SPREAD-DIMCAD findings show that the opposite is true in diabetes: How matters. There is more to stroke and MI prevention than just glucose control.

The authors note that metformin may confer antiatherogenic benefit beyond its hypoglycemic action through reduction of coagulation, inflammation, and endothelial dysfunction. Metformin is weight-neutral, but the weight lost by the metformin group and gained by the glipizide group during the trial is unlikely to have played an important role in the outcome.

The practice implications of this high-quality RCT are limited because there is nearly universal consensus that metformin is the drug of first choice in type 2 diabetes. In the UK Prospective Diabetes Study (UKPDS 34), metformin monotherapy was associated with a 36% reduction in all-cause mortality at 10.7 years compared with diet alone. SPREAD-DIMCAD extends the generalizability of UKPDS 34 to high-risk patients.