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

Background: Effective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications. Methods: The DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy. Findings: During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0·73, 95% CI 0·65-0·83; p