Results of the U.S. Diabetes Prevention Program (DPP) were first published in 2002 in the New England Journal of Medicine, describing the effects of standard lifestyle recommendations combined with either placebo or metformin, in comparison to a more intensive lifestyle program (which included calorie/fat reduction and exercise, designed to induce at least 7% weight loss) on people at high risk for developing type 2 diabetes (T2D). The initial results, published with an average follow-up of nearly 3 years for over 3,000 participants, suggested that both metformin and intensive lifestyles changes were more effective than standard recommendations, both in the reduction of T2D incidence and the delay in its development. Lifestyle interventions reduced the incidence of T2D by 58% compared to 31% with metformin (both compared to placebo).
The Lancet Diabetes & Endocrinology has recently published a 21-year follow-up of this study, with some modifications to the protocol, now known as the DPP Outcomes Study (DPPOS). The placebo was discontinued, and participants in both the metformin and placebo groups received a modified lifestyle program (based on the intensive program) for 6 months. Metformin was continued open-label by people who had been taking it previously, and all participants received quarterly lifestyle classes (the intensive lifestyle group also received semiannual group classes).
After an average of 21 years, the intensive group had a 24% lower incidence of T2D and a median delay in T2D diagnosis of 3.5 years, while the original metformin group had a 17% lower incidence and a 2.5-year delay. Improvements were found across all subgroups, especially among people with a higher baseline fasting glucose or HbA1c. This long-term reduction in diabetes incidence was largely attributed to reductions in risk that occurred in the original 3-year DPP trial, highlighting the importance and effectiveness of early intervention and prevention.