November 20, 2013
Metformin Doesn’t Lower Measure of Cardiovascular
Risk in Nondiabetics

Glasgow, Scotland—In patients with type 2 diabetes, metformin reduces cardiovascular risk seemingly independent of lowering blood glucose concentration, but a new study finds that the common diabetes drug failed to have similar effect in nondiabetic patients who had high cardiovascular risk and were taking statins.

Authors of the study, published recently in The Lancet, point out that metformin had no effect on carotid intima-media thickness (cIMT) and little or no effect on several surrogate markers of cardiovascular disease in the study group.

“There has been a lot of anticipation based on research in diabetic patients suggesting that metformin has cardiovascular benefits beyond its effects on blood glucose. We were hoping to find that it might also prevent hardening of the arteries, a warning sign for future heart attacks and strokes, in people without diabetes already on a statin,” explained study leader David Preiss, MRCP, from the University of Glasgow in the United Kingdom.

Background in the article notes that metformin works by reducing the overactive glucose production associated with diabetes, but it has also been shown to reduce other related risk factors for heart disease such as cholesterol levels and inflammatory and blood clotting markers in earlier studies conducted before the common use of statins. The report also discusses a previous UK trial finding that metformin treatment led to a 39% reduction in risk of heart attack over 10 years in diabetic patients.

This study, the Carotid Atherosclerosis: MEtformin for insulin ResistAnce (CAMERA) trial, was designed to investigate the effect of metformin on changes in cIMT in nondiabetic individuals with heart disease taking statins. For the research over 18 months, 86 patients were assigned to take 850 mg of metformin twice daily while 87 patients received a placebo.

After 18 months, no improvement in cIMT or the extent of atherosclerotic plaque in the carotid arteries was noted in patients taking metformin, with the average cIMT increasing significantly in both groups (0.024 mm per year for metformin, 0.017 mm for placebo), according to the results.

On the other hand, the patients using metformin showed significant reductions in all measures of adiposity—body weight [by more than 3 kg], body fat, body mass index, and waist circumference—compared with placebo. That is similar to what is often achieved on weight loss drugs, according to the authors, who also report improvements in other risk factors for the development of type 2 diabetes.

Overall, 251 adverse events were reported—136 in 63 patients taking metformin and 115 in 58 patients given placebo. Most common were gastrointestinal events such as diarrhea, nausea, and vomiting.

“Major cardiovascular outcome trials are needed to conclusively assess metformin’s cardiovascular effects in people without type 2 diabetes—such trials are underway at present,” Preiss said. “We cannot dismiss the potential cardiovascular benefit of metformin in patients without diabetes but CAMERA suggests that metformin has limited impact on important cardiovascular risk factors when patients are already on a statin.”

Writing in a linked comment, two researchers from the University Medical Center Groningen in the Netherlands caution, “The CAMERA study shows that the effect of metformin—in addition to current best treatment, including statins—on cIMT is probably small or negligible…[but] whether the primary endpoint of CAMERA or secondary endpoints such as HbA1c best represent cardiovascular outcome is unclear. The definitive evidence for the role of metformin in nondiabetic cardiovascular disease will have to be provided by large randomized clinical trials powered for cardiovascular outcomes such as the Glucose Lowering In Non-diabetic hyperglycemia Trial, in which 12 000 patients with high cardiovascular risk and dysglycemia but without diabetes, will be assigned to metformin or placebo for five years. Until then, the role of metformin for improving cardiovascular outcomes has promise, but is still largely unproven.”

U.S. Pharmacist Social Connect