Treatment of prediabetes with metformin or intensive lifestyle therapy for at least 3 years has no long-term benefits (Diabetes Prevention Program)

Reference

Goldberg RB, Orchard TJ, Crandall JP, et al, for the Diabetes Prevention Program Research Group. Effects of long-term metformin and lifestyle interventions on cardiovascular events in the diabetes prevention program and its outcome study. Circulation 2022;145(22):1632-1641.

Synopsis

The original Diabetes Prevention Program study randomized 3234 overweight or obese adults with impaired glucose tolerance ("prediabetes") to receive metformin 850 mg twice daily, an intensive exercise program, or placebo and followed them for 3 years. The primary outcome was the prevention of a diagnosis of type 2 diabetes mellitus (T2DM), which was reduced by 58% in the lifestyle therapy group and by 31% with metformin compared with placebo. Patients were invited to participate in a long-term open-label follow-up study, and 86% agreed. All patients were offered a less-intensive lifestyle intervention, and those who were originally randomized to receive metformin continued to take it until their glycated hemoglobin level was 7.0% or higher, at which time their physician determined the appropriate drug therapy for T2DM. This article reports long-term cardiovascular and mortality outcomes for each group. Patients in the intervention groups were less likely to have been given a diagnosis of T2DM (55% for metformin and 53% for lifestyle vs 60% for placebo; P = .001; number needed to treat [NNT] = 17) and the lifestyle therapy group was also less likely to have hyperlipidemia (91% vs 94%; P = .03; NNT = 33). There was no difference between either intervention group and placebo with regard to the risk of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. There was also no significant difference in the composite of all 3 outcomes for the original metformin group versus the placebo group (hazard ratio [HR] 1.03; 95% CI 0.78 - 1.37) or for those in the original lifestyle group versus the placebo group (HR 1.14; 0.87 - 1.50). Subgroup analysis by age, sex, race, or the presence of T2DM found no reduction in risk for any group. There was a trend for women to have more composite endpoint outcomes with intensive lifestyle intervention, but with 24 subgroup comparisons this could just be due to chance. Limitations include that the study did not adjust for differences in medication use among groups, including the use of statins and other cardiovascular or diabetes medications prescribed by their physicians.