Rosiglitazone monotherapy improves glycaemic control in patients with type2 diabetes: a twelve-week, randomized, placebo-controlled study

Aim: Rosiglitazone is the most potent of the thiazolidinediones, a novel cl ass of oral antidiabetic agents that reduce blood glucose levels by sensiti zing peripheral tissues to insulin. This study was designed to identify dos es of rosiglitazone that would lower fasting plasma glucose (FPG) in patien ts with type 2 diabetes. Methods: In this 12-week, double-blind, multicentre study, 380 patients wit h FPG values greater than or equal to 7.8 mmol/L (140 mg/dL) and less than or equal to 13.3 mmol/L (240 mg/dL) were randomly assigned to receive treat ment with placebo or rosiglitazone, 0.05, 0.25, 1.0, or 2.0 mg twice daily. The primary efficacy parameter was changed in FPG from baseline after 12 w eeks of treatment. Secondary endpoints were changes in HbA1c, fructosamine, C peptide, insulin, lipid levels, and body weight (b.w.). Safety monitorin g included clinical laboratory evaluations, electrocardiography, and echoca rdiography. Results: Rosiglitazone 1.0 and 2.0 mg b.i.d. produced significant decreases in FPG (p=0.0001). Fructosamine also decreased in patients treated with th ese two dosages (p=0.003 in the 2.0 mg b.i.d. group). Rosiglitazone 2.0 mg b.i.d. significantly reduced plasma insulin levels (p=0.0044) and free fatt y acids (p=0.0014) compared with placebo. Total cholesterol (p=0.0001), HDL (p=0.0009), and LDL (p=0.0001) increased in the rosiglitazone 2.0 mg b.i.d . group, but there was no significant change in the total cholesterol/HDL r atio or triglyceride levels in any rosiglitazone treatment group. Clinicall y insignificant dose-dependent increases in b.w. were observed in the rosig litazone 1.0 and 2.0 mg b.i.d. treatment groups. Conclusions: Twelve weeks of treatment with rosiglitazone 2.0 mg b.i.d. sig nificantly decreases fasting plasma glucose, fructosamine, plasma insulin, and free fatty acids in patients with type 2 diabetes. Longer studies using higher doses will be needed to assess the efficacy and safety of rosiglita zone in patients with type 2 diabetes mellitus.