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Lifestyle Changes Superior to Metformin for Diabetes Prevention

Exercise and diet trumps medication in prevention of diabetes in high-risk patients

The Diabetes Prevention Program (DPP) study took place between 1996 and 2001. This randomized trial showed that lifestyle intervention was more effective at preventing or delaying onset of type 2 diabetes.

Almost 3,000 subjects from the original trial were followed until 2014 for the DPP Outcomes Study. In this placebo-controlled continuation of the study, patients were assigned to an intensive lifestyle intervention or to metformin 850 mg twice daily. Another group received a placebo intervention. Lifestyle intervention included a low-fat, low-calorie diet, and 15 minutes of moderate-intensity exercise per day. The lifestyle group saw a greater reduction in diabetes incidence at 27% (hazard ratio 0.73, 95% CI 0.65-0.83; p<0.0001) compared to 18% in the metformin group (hazard ratio 0.82, 95% CI 0.72-0.93;p=0.001). By follow-up year 15, the differences in diabetes incidence were muted, but still significant: 55% of the lifestyle group, 56% of the metformin group, and 62% of the placebo group had diabetes.

The study authors also examined prevalence of microvascular disease, defined as an aggregate of nephropathy, retinopathy, and neuropathy examined via changes in the blood vessels. They did not find a statistically significant difference between the groups overall. However, among women, the lifestyle intervention had lower incidence of microvascular complications (hazard ratio 8.7%, 95% CI 7.4-10.2) than the metformin group (hazard ratio 11.2%, 95% CI 9.7-12.9) and placebo group (hazard ratio 11.0%, 95% CI 9.6-12.6). The participants who did not develop diabetes had a 28% lower incidence of these complications than those who did, however (relative risk 0.72, 95% CI 0.63-0.83;p<0.0001).

The results of this study illustrate a couple important points for practice. First of all, lifestyle changes are superior to metformin for prevention or delay of diabetes in high-risk patients. Second of all, prevention of diabetes is important for halting of microvascular disease, irrespective of method used to prevent diabetes. The study’s results line up with American Diabetes Association guidelines, which state that lifestyle changes should remain first-line for prevention, and metformin should be used for younger and more obese patients.

Practice Pearls:

  • Lifestyle interventions, comprising dietary and physical activity improvements, are superior to metformin for prevention of diabetes.
  • Neither lifestyle interventions nor metformin have a statistically significant impact on prevention of microvascular disease overall, although preventing diabetes itself does.
  • Lifestyle intervention did result in a statistically significant reduction of microvascular disease versus metformin and placebo for women only.

Diabetes Prevention Program Research Group. “Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study.” Lancet Diabetes Endocrinol. 2015