CAMERA in Print: No Plaque Changes with Metformin on Statins

Shelley Wood

November 07, 2013

BARCELONA, SPAIN — A single-center, randomized trial showing that metformin on top of statins does not slow the progression of cardiovascular disease in high-risk patients without diabetes has now been published[1].

As reported by heartwire when it was presented at the EASD 2013 meeting, the study enrolled 173 patients with stable coronary artery disease and large waist circumference. After 18 months, the combination of metformin and a statin showed no improvements in carotid intima-media thickness (CIMT) progression or change in carotid plaque score; it also failed to show improvements in cholesterol and fasting glucose levels.

The trial did, however, show that the 86 patients randomized to receive metformin on top of a statin lost a mean of 3.2 kg, whereas the statin-only group lost none. There were also significantly greater declines in body-mass index (BMI) in the metformin group.

Lead investigator Dr David Preiss (University of Glasgow, Scotland), who spoke with heartwire when he presented trial results in Barcelona, said at the time that the "impressive" weight loss seen in the metformin group warrants exploring further. "You wouldn't dismiss [metformin's] chances based on our study alone," he said.

The Carotid Atherosclerosis: Metformin For Insulin Resistance (CAMERA) trial is published online November 7, 2013 in Lancet Diabetes & Endocrinology.

The rationale for CAMERA came from previous observations, including the UKPDS study, that metformin reduced not only diabetes end points, but also MI. Moreover, the CVD benefits appeared to be unrelated to glycemic improvement.

Preiss and others are now looking to larger trials for better answers. The GLINT study, now under way, is a multicenter CV primary-prevention trial with a planned enrollment of 12 000 nondiabetic subjects. Participants will have to have a predicted 10-year risk of CVD of 20% (by Framingham) and a high-normal HbA1c; they are being randomized to either metformin or placebo, with a follow-up of five years.

In a Comment accompanying CAMERA's publication[2], Drs Chris PH Lexis and Iwan CC van der Horst (University Medical Center Groningen, the Netherlands) write that "definitive evidence for the role of metformin in nondiabetic CVD will have to be provided by large randomized trials powered for CV outcomes," like GLINT. "Until then, the role of metformin for improving cardiovascular outcomes has promise but is still largely unproven."

Preiss, in September, pointed heartwire to two smaller studies that may also provide some insights: one is REMOVAL , a 500-patient, multinational study looking at add-on metformin in type 1 diabetes, with an end point of change in CIMT. Another is GIPS III , a Dutch study of 380 post-STEMI patients, looking at the ability of metformin to reduce progression to heart failure.

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