Metformin no help for CHD patients without diabetes

Cardiovascular Disease
Cardiovascular Disease

HealthDay News -- Metformin does not appear to have cardiovascular benefits for nondiabetic patients with established heart disease, results of the CAMERA study indicate.

Mean distal carotid intima-media thickness, a surrogate marker for astherosclerotic disease, increased at similar rates among patients taking metformin and those assigned to placebo through 18 months of treatment, David Preiss, PhD, from the University of Glasgow in the United Kingdom, and colleagues reported in Lancet Diabetes & Endocrinology.

There were also no differences between the groups in total, HDL or non-HDL cholesterol, triglycerides, high-sensitivity C-reactive protein or fasting glucose, despite lower HbA1c, fasting insulin, HOMA-IR and tissue plasminogen activator in the metformin-treated patients, the researchers found.

They conducted a single-center, double-blind placebo-controlled trial involving 173 patients taking statins, who did not have type 2 diabetes, but did have coronary heart disease and large waist circumference. The participants were randomly assigned to metformin (86 patients) or matching placebo (87 patients). Progression of mean distal carotid intima-media thickness over 18 months was the primary end point.

The average distal carotid intima-media thickness assessed by ultrasound increased at an annual rate of 0.024 mm in the metformin group and 0.016 mm in the placebo group, a nonsignificant difference (P=0.29). Similarly, there was no difference between the groups in the change in the carotid plaque score (P=0.89). 

Overall there were similar rates of adverse events in the metformin vs. placebo groups (74% vs. 69%), although cases of diarrhea, nausea and vomiting were more common in the metformin group (28 vs. five total cases).

The rate of combined cardiovascular disease events (including myocardial infarction, stroke, coronary revascularization, unstable angina or cardiovascular death) were similar among the metformin and placebo groups (7% vs. 5%, respectively), with only 10 patients total experiencing at least one cardiovascular event.

"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 (GLINT), in which 12,000 patients with high cardiovascular risk and dysglycemia but without diabetes will be assigned to metformin or placebo for 5 years," Chris Lexis, MD, and Iwan van der Horst, MD, of the University of Groningen in The Netherlands, wrote in an accompanying editorial. "Until then, the role of metformin for improving cardiovascular outcomes has promise, but is still largely unproven."

Limitations to the current study included a relatively high number of patients who stopped treatment or lowered doses over the study period, and the use of multiple statistical tests.

References

  1. Preiss D et al. Lancet Diabetes & Endocrinology. 2013; doi: 10.1016/S2213-8587(13)70152-9.
  2. Lexis C, van der Horst I. Lancet Diabetes & Endocrinology. 2013; doi:10.1016/S2213-8587(13)70171-2.

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