Aim: The second-generation thiazolidinediones (TZDs), rosiglitazone and pioglitazone, significantly decrease fasting plasma glucose and glycosylated haemoglobin (HbA(1c)) levels in patients with diabetes. Recent studies suggest that early treatment with TZDs may prevent the progression from insulin resistance (IR) to type 2 diabetes mellitus (T2DM). This prospective analysis examined the effect of early TZD treatment in the prevention or delay of T2DM in a multiethnic population with impaired glucose tolerance (IGT) and IR.
Methods: The analysis included 172 patients (aged 29-86 years) with IGT and IR (normal or borderline HbA(1c), C-peptide levels > 2 mg/ml, fasting blood sugar 100-125 mg/dl, and 2-h postprandial blood glucose levels 140-200 mg/dl). Patients in the active treatment group (n = 101) had received troglitazone for an average of 10 months before being randomly switched to rosiglitazone (4 mg/day) or pioglitazone (30 mg/day). Patients were switched when troglitazone was withdrawn from the US market because of liver toxicity concerns. Patients with IGT and IR who received no antidiabetic medication served as a control group (n = 71). HbA(1c) and C-peptide levels were measured at baseline (2 years) and study end point (3 years). Kaplan-Meier testing, using time to outcome as the main outcome variable, determined risk reduction in the TZD group relative to the control group.
Results: Mean HbA(1c) and C-peptide levels decreased for patients receiving either TZD at the 2-year assessment, and reductions were maintained at study end point. After 2 years, none of the patients receiving TZD therapy progressed to T2DM; three patients progressed to T2DM by study end point. In the control group, 11 patients became diabetic after 2 years and 19 patients became diabetic by the end of the study. The incidence (risk reduction) of diabetes after 3 years was 88.9% lower in the TZD group compared with the control group (p < 0.001).
Conclusions: The TZDs, rosiglitazone and pioglitazone, were effective in reducing HbA(1c) and C-peptide levels in patients with IGT/IR. Progression of IR/IGT to T2DM appears to be significantly delayed or prevented with early TZD treatment.