Issue 214 Item 4 Metformin Effective for Diabetes Prevention

Three studies have shown that Metformin can help prevent type 2 diabetes in individuals at high risk of developing the disease. But exercise shown to be the drug of choice According to Donald L. Sullivan, PhD, RPh, and Aleda M. Hess, Pharm D, both of Ohio Northern University, new studies must evaluate its long-term safety, efficacy, cost-effectiveness.

Metformin targets insulin resistance by increasing the sensitivity of insulin receptors in muscle tissue, and it is also known to decrease hepatic glucose production. Some researchers have hypothesised that the drug may help prevent type 2 diabetes. To address this hypothesis, Dr. Sullivan and colleagues identified and evaluated studies that have examined the effect of metformin on diabetes prevention.

Their search identified three relevant studies. The earliest study (Fontfonne et al. Diabetes Care 1996) examined the efficacy of metformin in preventing insulin resistance syndrome in 324 adults with upper body obesity. After 1 year of treatment, patients receiving metformin experienced a significantly lower increase in fasting blood glucose levels compared with the placebo group (3.6 mg/dL vs. 7.2 mg/dL, P < .05).

"These results are limited, yet showed the need for a larger clinical study to prove metformin’s preventative effects," Drs. Sullivan and Hess write.

A second study examined the effects of metformin in preventing type 2 diabetes in 29 adolescent who had pre-existing factors of this disease (Freemark et al. Pediatrics 2001). After 6 months of treatment, patients receiving metformin showed a significant decline in fasting blood glucose levels (84.9 to 75.1 mg/dL, P < .02) and a 0.5 kg/m² decrease in body mass index (BMI), whereas the placebo group showed no change in fasting blood glucose and a 0.9 kg/m² increase in BMI. However, the authors note that the study was limited by its small sample size and short duration.

The largest study identified in the search was reported by the Diabetes Prevention Program Research Group (N Engl J Med 2002 Feb 7;346(6):393-403). The study randomised 3234 individuals who were considered to be at risk of developing diabetes into 3 treatment categories: 1) metformin 850 mg twice daily and diet and exercise recommendations, 2) placebo twice daily and lifestyle recommendations, and 3) lifestyle recommendations only. After 2.8 years of therapy, incidence of type 2 diabetes was 58% lower in the group with radical lifestyle changes only and 31% lower in the metformin group compared with the placebo group.

Taken together, Drs. Sullivan and Hess propose that the studies show some potential for metformin in the treatment of the prediabetic condition. Although exercise may be a more effective prevention method, he suggests that the drug could potentially serve as an alternative choice for patients who are unwilling to commit to or maintain radical lifestyle changes.

They caution, however, that long-term data from a larger population are needed before advocating the use of metformin in this capacity. Ann Pharmacother 2004 Jul;38(7):1283-1285. Epub 2004 May 18

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