Type 2 diabetes affects over 150 million adults worldwide and this figure is expected to double over the next 25 yr. This increase will be accompanied by a marked increase in the number of patients with ESRD due to diabetes. We hypothesized that a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes We randomly assigned 3234 nondiabetic persons with elevated fasting and postload plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7% weight loss and at least 150 min of physical activity per week. The mean age of the participants was 51 yr, and the mean body mass index was 34.0 kg/m(2); 68% were women, and 45% were members of non-Caucasian racial/ethnic groups. The average follow-up was 2.8 yr. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence of diabetes by 58% (95% CI: 48 to 66%) and metformin by 31% (95% CI: 17 to 43%), compared with placebo; the lifestyle intervention was significantly more effective than metformin. In conclusion, lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk and the lifestyle intervention was more effective than metformin. Because the lifestyle changes worked equally in all racial/ethnic groups in the Diabetes Prevention Program, they should be applicable to high-risk populations worldwide and may be able to reduce the projected progressive rise in the incidence of diabetes and the expected increase in ESRD.