Moderate exercise and improved diet, accompanied by a small weight loss, have proven efficacy in the treatment of mild hypertension. Members of the Diabetes Prevention Program Research Group extended that logic to the management of patients with impaired glucose tolerance, who are at increased risk of developing diabetes.

The group enrolled 3,234 study participants with impaired glucose tolerance (a fasting glucose level of 95 to 125 mg per dL [ 5.3 to 6.9 mmol per L] and a two-hour postprandial glucose level of 140 to 199 mg per dL [7.8 to 11.0 mmol per L] after a 75-g glucose load) who were randomly assigned to receive metformin in a dosage of 850 mg twice daily, placebo, or a lifestyle modification program.

The mean age of the subjects was 51 years, female participants constituted 68 percent of the total, and 45 percent were from ethnic minority groups. The enrollees were substantially overweight, with a mean body mass index of 34 (e.g., a weight of 205 lb for a subject who was 5 ft, 5 in).

The lifestyle modification intervention involved a one-on-one review of a 16-lesson curriculum over the first 24 weeks of the program, followed by monthly reinforcement sessions. Modification goals included at least 150 minutes of moderate exercise (e.g., brisk walking) per week, weight loss of at least 7 percent, and compliance with a low-calorie, low-fat diet. The mean length of follow-up was 2.8 years.

Study participants were checked for progression to diabetes through fasting glucose tests every six months and an annual glucose tolerance test. The weight-loss goal was achieved by 50 percent of participants and sustained by 38 percent of those in the modification group. The exercise target was maintained by 58 percent of modification subjects during the follow-up period. Metformin was taken at the full intended dosage of 850 mg twice daily by 84 percent of assigned subjects, the others took the pill only once daily because of gastrointestinal side effects.

The estimated cumulative incidence of progression to diabetes was 28.9 percent in the placebo group, 21.7 percent in those taking metformin, and 14.4 percent of those in the lifestyle modification group. The number needed to treat (how many persons would have to follow their assigned intervention for three years to prevent diabetes in one subject) was 6.9 for lifestyle modification and 13.9 for metformin.

The investigators conclude that lifestyle changes and metformin therapy reduce the risk of progression to diabetes in at-risk patients, with lifestyle modification demonstrating the more powerful effect.