Metformin may not offer cardiovascular benefits

Although research has suggested some cardiovascular benefit to the glucose-lowering drug metformin, a study published online Nov. 7 in The Lancet found that the drug had no effect on carotid intima-media thickness (cIMT) and little to no effect on other cardiovascular disease markers in patients who are at high risk for cardiovascular disease who take statins but do not have diabetes.

The purpose of the CAMERA study (Carotid Atherosclerosis: Metformin for insulin ResistAnce) was to determine the effect on metformin (Glucophage, Bristol-Myers Squibb) on cIMT progression in people with coronary heart disease who do not have diabetes.

The researchers randomized 173 non-diabetic patients to either the metformin group or the placebo group. The patients had coronary heart disease and, per guidelines, were taking statins. The primary endpoint was progression of cIMT over 18 months. Secondary outcomes included change in carotid plaque score, glycemia indicators, insulin concentrations, insulin resistance (measured using the Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]) and concentrations of lipids, high sensitivity C-reactive protein (CRP) and tissue plasminogen activator (tPA). 

Average baseline cIMT was 0.717 mm and average carotid plaque score was 2.43. There was no significant difference in cIMT progression between the two groups. The change in carotid plaque score also did not differ significantly between the two groups.

The metformin group had better glucose control and lower tPA, but did not differ significantly from the placebo group in cholesterol, triglycerides, high sensitivity CRP or fasting glucose.

Based on their findings, the authors concluded that it is too soon to consider metformin for cardiovascular disease.

“Further evidence is needed from large trials of cardiovascular outcomes before metformin can be recommended for cardiovascular benefit for non-diabetic patients with high cardiovascular risk who are being treated with statins,” wrote the authors, led by David Preiss, PhD, of the University of Glasgow in the U.K.

In accompanying editorial, Chris P.H. Lexis, MD, and Iwan C.C. van der Horst, MD, of the University of Groningen in Groningen, The Netherlands, questioned whether CAMERA’s primary endpoint was the best measure of cardiovascular outcome.

They argued that other ongoing trials may help clarify the role of metformin in non-diabetic patients with cardiovascular disease. “Until then, the role of metformin for improving cardiovascular outcomes has promise, but is still largely unproven.” they wrote.