Diabetes Dateline
Winter 2009

Metformin May Protect against Death from Type 2 Diabetes-related Cardiovascular Disease

Metformin, a medication to control type 2 diabetes, is moderately protective against cardiovascular disease (CVD) mortality, according to a meta-analysis funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Researchers at the Johns Hopkins Evidence-based Practice Center analyzed data from 40 reports on controlled clinical trials of oral diabetes medications. Drug classes evaluated included thiazolidinediones, second-generation sulfonylureas, meglitinides, and biguanides such as metformin. All are widely used to lower levels of hemoglobin A1C (A1C), a 3-month average of blood glucose, also called blood sugar.

Maintaining an A1C of less than 7 percent is a broadly accepted therapeutic goal, based on evidence that it reduces eye, nerve, and kidney complications of diabetes. Evidence is scant, however, on the effects of oral type 2 diabetes medications on major CVD events such as heart attack or stroke.

“It is unclear how these agents compare with respect to long-term cardiovascular risk,” Elizabeth Selvin, Ph.D., M.P.H., assistant professor of epidemiology, the Johns Hopkins University, and colleagues write in their report, which appears in the October 31, 2008, issue of Archives of Internal Medicine. As opposed to looking at effects on CVD risk factors such as changes in A1C, serum blood lipids, and blood pressure, the authors examined hard clinical outcomes, such as heart attack, stroke, and death.

Searching peer-reviewed literature published from 1966 to 2005, the researchers limited their meta-analysis to oral medications that were available January 2006 and that reported all-cause mortality and cardiovascular morbidity and mortality. They excluded studies that examined combination therapies of more than two oral diabetes medications, that lasted less than 3 months, or that had fewer than 40 participants.

Based on pooled data from six clinical trials representing more than 11,000 individuals, metformin compared with any other oral diabetes medication or placebo was the only agent that significantly reduced CVD mortality. Metformin also decreased all-cause mortality and CVD morbidity, but the data were not significant.

The authors urge more long-term studies to better ascertain the risks and benefits of the growing number of available oral medications for type 2 diabetes. They also urge better reporting of CVD events in short-term studies.

To read the full-text article, go to http://archinte.ama-assn.org/cgi/content/full/168/19/2070.

For information about the Johns Hopkins Evidence-based Practice Center, visit www.jhsph.edu/epc/index.html.

NIH Publication No. 09–4562
March 2009

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