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Metformin failed to improve CV risk factors in patients without diabetes
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New data show that metformin did not significantly affect progression of carotid intima-media thickness, carotid plaque score or other markers of cardiovascular disease in patients without diabetes who were being treated with statins.
In the single-center, double blind CAMERA trial, David Preiss, PhD, of the University of Glasgow in the United Kingdom, and colleagues randomly assigned 173 patients without diabetes (mean age, 63 years) to metformin 850 mg twice daily (n=86) or placebo (n=87) for 18 months. All patients had coronary heart disease, large waist circumferences and were being treated with statin therapy. Baseline mean carotid intima-media thickness (cIMT) and carotid plaque scores were 0.717 mm and 2.43 mm, respectively.
After 18 months, the researchers observed significant increases in cIMT in both the metformin (0.024 mm per year; 95% CI, 0.014-0.033) and placebo (0.017 mm per year; 95% CI, 0.008-0.026) groups, but they found no significant difference in rates of cIMT progression between groups (slope difference, 0.07 mm per year; 95% CI, –0.006 to 0.2). Similarly, changes in carotid plaque scores were not significantly different between groups (slope difference, 0.01 per year; 95% CI, –0.23 to 0.26).
Metformin yielded improvements in some measures, as compared with placebo. Patients in the metformin group experienced significant reductions in HbA1c, log fasting insulin concentration, log homeostasis model assessment of insulin resistance (HOMA-IR) and tissue plasminogen activator. Results also revealed significant decreases in all measures of adiposity, including body weight, body fat, BMI and waist circumference, in the metformin group compared with the placebo group (P<.0001 for all).
The researchers, however, found no significant differences in total cholesterol, HDL, non-HDL, triglycerides, high sensitivity C-reactive protein or fasting glucose between the metformin and placebo groups.
In the metformin group, 138 adverse events occurred in 64 patients vs. 120 adverse events in 60 patients in the placebo group. Twenty-eight patients in the metformin group vs. five in the placebo group experienced diarrhea and nausea or 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 in a press release. “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.”
In an accompanying comment, Chris P.H. Lexis, MD, and Iwan C.C. van der Horst, MD, PhD, both from the University of Groningen in the Netherlands, also warned against drawing firm conclusions from these data.
“Whether the primary endpoint of CAMERA or secondary endpoints such as HbA1c best represent cardiovascular outcome is unclear,” they wrote. “The definitive evidence for the role of metformin in non-diabetic 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 5 years. Until then, the role of metformin for improving cardiovascular outcomes has promise, but is still largely unproven.”
For more information:
Lexis CPH. Lancet. 2013;doi:10.1016/S2213-8587(13)70171-2.
Preiss D. Lancet. 2013;doi:10.1016/S2213-8587(13)70152-9.
Disclosure: See the study for a list of the researchers’ financial disclosures. Lexis and van der Horst are investigators of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Intervention in ST-Elevation Myocardial Infarction Trial.