The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The NIDDK presciently proposed the Diabetes Prevention Program (DPP), a multi-center randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin compared with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After a mean of 2.8 years, ILS reduced diabetes risk by 58% and metformin by 31%, leading to study termination ahead of schedule due to demonstrated efficacy of both interventions. In 2002, an extension of the DPP study, the DPP Outcomes Study (DPPOS), was initiated to examine the longer-term course and consequences of diabetes prevention. Over 21 years of median total follow-up, compared with placebo, cumulative diabetes incidence was reduced by 24% and 17% in the original ILS and metformin groups, respectively, with increases in median diabetes-free survival of 3.5 and 2.5 years/person. During long-term follow-up, there were no significant effects of the original DPP interventions on microvascular or cardiovascular outcomes. However, compared with participants who progressed to diabetes, those who didn’t progress had a significantly lower prevalence of microvascular outcomes. Longer term follow-up of the cohort continues to examine relationships between diabetes and prediabetes and an expanded array of diabetes and aging-related morbidities.
Funding
Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award numbers U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400, by providing funding during DPP and DPPOS to the clinical centers and the Coordinating Center for the design and conduct of the study, and collection, management, analysis, and interpretation of the data. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the National Cancer Institute, the Office of Research on Women’s Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Merck KGaA provided medication for DPPOS. DPP/DPPOS have also received donated materials, equipment, or medicines for concomitant conditions from Bristol-Myers Squibb, Parke-Davis, and LifeScan Inc∙, Health O Meter, Hoechst Marion Roussel, Inc∙, Merck-Medco Managed Care, Inc∙, Merck and Co∙, Nike Sports Marketing, Slim Fast Foods Co∙, and Quaker Oats Co. McKesson
