Ethnicity-associated variance in efficacy of pioglitazone as a preventive tool

Ramachandran, A. et al. Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2). Diabetologia 52, 1019–1026 (2009).

Pioglitazone therapy does not add extra benefit to lifestyle modification for prevention of type 2 diabetes mellitus in people in India who are at risk of developing the disease. This finding differs from results that were obtained in similar studies performed in the US.

Thiazolidinediones, such as pioglitazone and rosiglitazone, increase insulin sensitivity and are efficient for treatment of patients with diabetes mellitus in various ethnic groups. In a US-based study, pioglitazone was also effective in reducing the risk of type 2 diabetes mellitus in individuals with impaired glucose tolerance. Ramachandran and colleagues assessed whether combination of this drug with a lifestyle modification program, the efficacy of which has already been established in epidemiological studies, is more effective in preventing diabetes mellitus than lifestyle changes alone.

In a population-based, double-blind study, 407 Asian Indian adults (mean age 45.3 ± 6.2 years; mean BMI 25.9 ± 3.3 kg/m²) with persistently impaired glucose tolerance were sequentially assigned to receive either advice on lifestyle modification (including healthy diet and regular exercise) and pioglitazone therapy 30 mg per day, or the same advice and placebo (204 and 203 participants, respectively). After 3 years, the cumulative incidence of type 2 diabetes mellitus and the number of participants with normoglycemia did not differ significantly between the two study groups, which implies that addition of pioglitazone did not improve the beneficial effects of lifestyle modification.

The authors suggest that the differences between these results and those that were obtained in American patients might be partly attributable to ethnic differences in nondiabetic patients' response to pioglitazone therapy. Such differences are also known to exist in the susceptibility to insulin resistance and type 2 diabetes mellitus—both are higher in the Indian population than in the US population.