Type 2 Diabetes Prevention Studies

• Both behavioral and pharmacologic approaches to treating insulin resistance have been used to reduce the incidence of type 2 diabetes in high-risk individuals.
• The Finnish Diabetes Prevention Study compared an intensive diet plus exercise program to simple follow-up in Finnish adults with impaired glucose tolerance (IGT). After 1 year, weight reduction was greater (-4.6 kg) in the intervention group than in the control group (P<0.0001). The intervention group also showed significant reductions in 2-hour glucose, fasting and 2-hour insulin, systolic and diastolic blood pressure, and serum triglycerides. After a mean follow-up of 3.2 years, people randomized to the lifestyle intervention had a 58% reduction in the risk of diabetes.
• One treatment arm of the US Diabetes Prevention Program (DPP) used a behavioral approach similar to that used in the Finnish study. Adults with IGT and fasting glucose >95 mg/dL were randomized to intensive lifestyle modification. A control group received minimal diet and exercise education (details of the interventions on following slides). After a median follow-up of 3 years, the intensive lifestyle group had a 58% reduction in the risk of diabetes compared to the control group.
• The Troglitazone in Prevention of Diabetes (TRIPOD) study evaluated diabetes incidence rates and b-cell function in Hispanic women with a history of gestational diabetes. Women were assigned to placebo or 400 mg/day troglitazone. After a median follow-up of 30 months, women randomized to troglitazone had a 55% reduction in the risk of diabetes. Protection from diabetes persisted when women were retested 8 months after stopping study medications. b-cell function was preserved for 4.5 years by troglitazone treatment, providing evidence for true diabetes prevention during that period.
• A separate arm of the US DPP was given metformin 850 mg bid. That group's diabetes rate was reduced 31% compared with the placebo group. No data on diabetes rates after stopping metformin were reported; therefore, it is not clear whether the drug simply lowered glucose levels (delay in diabetes) or truly altered the pathobiology of the disease (prevention, as seen in the TRIPOD study).
• The STOP-NIDDM randomized trial assessed the effect of acarbose in preventing or delaying conversion of IGT to type 2 diabetes based on a yearly oral glucose tolerance test. 714 patients with IGT were allocated to 100 mg acarbose and 715 to placebo three times daily. Of the acarbose-treated group, 221 (32%) patients developed diabetes compared with 285 (42%) patients in the placebo group (relative hazard 0.75 [95% CI 0.63-0.90]; P=0.0015). In addition, acarbose significantly increased reversion of IGT to normal glucose tolerance (P<0.0001). Study authors concluded that acarbose could be used as an alternative or in addition to changes in lifestyle to delay development of type 2 diabetes in patients with IGT.4 

Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350. 
Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.
Buchanan TA et al. Diabetes. 2002;51:2796-2803. 
Chiasson JL et al. Lancet. 2002;359:2072-2077.