Issue 119 Item 3 Three Drugs Show Useful in Prevention of Type 2 Diabetes

Three drugs have been shown to prevent or delay the onset of type 2 diabetes in people with impaired glucose tolerance, speakers said at the same Novartis Pharmaceuticals–sponsored symposium. The agents are:

Metformin. The landmark Diabetes Prevention Program (DPP) clearly showed that metformin works better than placebo, but not as well as intensive diet and exercise, Dr. Steven Kahn said.

The study randomized 3,234 people with impaired glucose tolerance to placebo, metformin (850 mg twice daily), or an intensive lifestyle modification program that included a low-calorie, low-fat diet and at least 150 minutes of exercise a week. At a mean follow-up of 2.8 years, the incidence of diabetes was 11% per year with placebo; the relative risk reduction was 31% with metformin and 58% with lifestyle modification (N. Engl. J. Med. 346[6]:393-403, 2002).

Lifestyle intervention worked in all age, gender, body composition, and ethnic groups. Metformin worked better in younger and heavier individuals. In fact, it was no better than placebo in the leanest subjects, said Dr. Kahn of the University of Washington, Seattle.

Still-unpublished DPP data on blood pressure and lipids also place metformin second to lifestyle intervention on most measures, he said.

Acarbose. In the Study to Prevent Non–Insulin-Dependent Diabetes Mellitus (STOP-NIDDM), funded by Bayer AG, 1,429 subjects aged 40-70 years with impaired glucose tolerance were randomized to receive 100 mg acarbose or placebo three times daily for a mean 3.3 years of follow-up. Discontinuation due to adverse events—mainly flatulence, diarrhea, and abdominal pain—was 19% with acarbose and 5% with placebo (Lancet 359[9323]:2072-77, 2002).

Most of the discontinuations occurred in the first year, said Dr. Jean-Louis Chiasson, professor of medicine at the University of Montreal.

Diabetes developed in 41.5% of placebo subjects, compared with just 32.4% of those on acarbose, for a 25% relative risk reduction.

Troglitazone. In the Troglitazone in the Prevention of Diabetes (TRIPOD) study, 235 Hispanic women diagnosed with gestational diabetes during the previous 4 years were randomized to placebo or 400 mg troglitazone daily. At 60 months, the number of patients with type 2 diabetes was 50% with placebo vs. 19% with troglitazone—a 55% relative risk reduction, said Dr. Thomas A. Buchanan, professor of medicine, obstetrics and gynecology, physiology, and biophysics at the University of Southern California, Los Angeles.

Results of TRIPOD are due to be published this fall in Diabetes, but troglitazone is no longer on the market. An open-label trial of another thiazolidinedione, the Pioglitazone in the Prevention of Diabetes study, has started enrolling women who completed TRIPOD. That trial will last 4 years.