Since the clinical trial began in 2002, 5,145 volunteers with type 2 diabetes who were 45-76 years of age and overweight or obese (body mass index > 25 kg/m2) have been recruited and enrolled in either the intensive lifestyle intervention (ILI) program or the diabetes support and education (DSE) program. The Diabetes Epidemiology and Clinical Research Section clinics enrolled 244 of these participants. The study has reported success in achieving and maintaining weight loss in the ILI group, while there was little weight loss on average in the DSE group. During the first four years after enrollment, the average weight losses were 6.2% in the ILI group and 0.9% in the DSE group. This successful weight loss means that it is possible to determine if weight loss has long-term health benefits in adults with type 2 diabetes. On the advice of the external data and safety monitoring board, the NIDDK discontinued the ILI owing to lack of a significant effect on cardiovascular disease events, the study's primary outcome. Participant follow-up continues to assess long-term health outcomes. There appeared to be many health benefits, however, other than the lack of effect on the primary outcome. The incidence rate of advanced kidney disease was reduced by 31% by the ILI, and health care costs were lower in this intervention arm. Analyses and reporting of other outcomes is underway. Genetic associations with weight loss in response to the intervention and to weight regain are analyzed.