The Diabetes Prevention Program (DPP) is a clinical trial that investigated whether modest weight loss through dietary changes and increased physical activity or treatment with the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in high risk individuals with prediabetes.

The study enrolled overweight persons with elevated fasting and post-load plasma glucose concentrations. Participants were randomized to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The primary outcome measure was development of diabetes, diagnosed on the basis of an annual oral glucose-tolerance test or a semiannual fasting plasma glucose test, according to the 1997 criteria of the American Diabetes Association: a value for plasma glucose of 126 mg per deciliter (7.0 mmol per liter) or higher in the fasting state, or 200 mg per deciliter (11.1 mmol per liter) or higher two hours after a 75-g oral glucose load. Participation in DPP continued after a diagnosis of diabetes was made, although study medication was discontinued and participants were sent to their local primary care provider for treatment of diabetes once fasting glucose was > 140 mg/dl.

Results showed that both lifestyle changes and treatment with metformin reduced the incidence of diabetes in persons at high risk compared with placebo. Furthermore, the lifestyle intervention was more effective than metformin in preventing the onset of diabetes.

Supplemental measurements were collected using biospecimens that were obtained during the original DPP clinical trial. These measurements included antibodies, biomarkers, hormones, and vitamin D levels to assess the relationships between sex hormones, diabetes risk factors, and the progression to diabetes. The supplemental data showed that sex hormones were associated with diabetes risk in men, but these associations were not found in women. Furthermore, obesity and glycemia were more important predictors of diabetes risk than sex hormones.

The primary goal of the DPP study was to compare the efficacy and safety of three interventions—an intensive lifestyle intervention, metformin, or placebo—in preventing or delaying the development of diabetes in high risk individuals. In addition, the study sought to assess differences between the three treatment groups in the development of cardiovascular disease and its risk factors; changes in glycemia, β-cell function, insulin sensitivity, obesity, physical activity, nutrient intake, and health-related quality of life; and occurrence of adverse events.

The primary outcome measure was development of diabetes, diagnosed on the basis of an annual oral glucose-tolerance test or a semiannual fasting plasma glucose test, according to the 1997 criteria of the American Diabetes Association: a value for plasma glucose of 126 mg per deciliter (7.0 mmol per liter) or higher in the fasting state, or 200 mg per deciliter (11.1 mmol per liter) or higher two hours after a 75-g oral glucose load. Secondary outcomes included cardiovascular risk profile and disease; and changes in glycemia, β-cell function, insulin sensitivity, renal function, body composition, physical activity, and nutrient intake, and health-related quality of life.

Eligibility criteria included:

• An age of at least 25 years
• A body-mass index of 24 or higher (22 or higher in Asians)
• A plasma glucose concentration of 95 to 125 mg/deciliter (5.3 to 6.9 mmol/liter) in the fasting state (≤125 mg/deciliter in the American Indian clinics)
• A plasma glucose concentration of 140 to 199 mg/deciliter (7.8 to 11.0 mmol/liter) two hours after a 75-g oral glucose load

Eligible persons were excluded if they were taking medicines known to alter glucose tolerance or if they had illnesses that could seriously reduce their life expectancy or their ability to participate in the trial.

The DPP study found that both lifestyle changes and treatment with metformin reduced the incidence of diabetes in persons at high risk; the lifestyle intervention proved more effective than metformin in preventing the onset of diabetes. These results suggest that that type 2 diabetes can be prevented or delayed in high-risk persons through weight loss, a diet low in fat and calories, and regular physical activity.

The supplemental data measurements demonstrated that sex hormones had predictive value for diabetes risk in men only. However, both obesity and glycemia were found to be stronger predictors of diabetes risk than sex hormones for both men and women.