Metformin Has No Heart Benefits in Nondiabetics

The recent single-center, double-blind, placebo-controlled CAMERA (Carotid Atherosclerosis: Metformin for Insulin Resistance) trial has shown that metformin has no cardiovascular benefits in nondiabetic individuals with coronary heart disease.

Metformin, a glucose-lowering drug, has demonstrated improved cardiovascular outcomes in patients with type 2 diabetes in previous trials, but its effects on cardiovascular outcomes in patients without diabetes is unknown. The CAMERA study was designed to explore the effects of metformin on the progression of mean carotid intima-media thickness (cIMT) in individuals with coronary heart disease but without diabetes.

“There are no other contemporary studies examining the potential cardiovascular benefit of metformin in a nondiabetic population,” said lead study author David Preiss, PhD, clinical senior lecturer and honorary consultant in metabolic medicine, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom, in an interview with Consultant360. “While metformin has been studied in nondiabetic individuals for other purposes, this was prior to the large-scale use of statins,” he added.

“Importantly, the key question we were asking was whether metformin could reduce cardiovascular risk when added to gold-standard therapy (ie, statins).” Researchers examined 173 nondiabetic patients (mean age, 63 years) with coronary heart disease and large waist circumferences who were taking statins. Participants were randomly assigned to either metformin 850 mg twice daily or placebo for 18 months.

Progression of mean distal cIMT was the primary endpoint; progression of carotid plaque score and change in measures of glycemia, and concentrations of lipids, high-sensitivity C-reactive protein, and tissue plasminogen activator were the secondary endpoints.

Preiss and colleagues found that progression of cIMT and change of carotid plaque score did not differ significantly between the two groups. While participants in the metformin group had lower HbA1c, insulin, Homeostasis Model Assessment of Insulin Resistance, and tissue plasminogen activator compared with those in the placebo group, there were no significant differences found between groups for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high-sensitivity C-reactive protein, or fasting glucose.

In addition, metformin significantly reduced all measures of adiposity, such as bodyweight, body fat, body mass index, and waist circumference compared with placebo. Average weight loss in the metformin group at 18 months was 3.2 kg compared with 0.0 kg in the placebo group.

“We wondered whether metformin might lead to weight loss—especially as this group of participants did not have diabetes—so we were surprised to see that metformin recipients lost as much as 3.2 kg compared to placebo recipients over only 18 months,” said Preiss. “CAMERA demonstrates that metformin is unlikely to meaningfully improve established cardiovascular risk factors on top of statins,” said Preiss.

“We should not dismiss its chances in a major trial, but it is unclear how metformin might reduce risk at this stage.” In terms of his recommendations for future research, Preiss explained that the next step would be a major trial “in which metformin’s effect on cardiovascular outcomes such as myocardial infarction is assessed.”

The GLINT (Glucose Lowering In Non-diabetic hyperglycaemia Trial) study, for example, will be examining the cardiovascular effects of taking metformin versus placebo for 5 years in approximately 12,000 nondiabetic patients with high cardiovascular risk and dysglycemia.

The Chief Scientist Office (Scotland) provided funding for the study, which was published online in The Lancet Diabetes & Endocrinology on November 7, 2013.

-Meredith Edwards White Reference Preiss D, Lloyd SM, Ford I, et al.

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. The Lancet Diabetes & Endocrinology. Early Online Publication, 7 November 2013. doi:10.1016/S2213-8587(13)70152-9