J Patel1, R J Anderson, E B Rappaport. 1. Clinical Research and Development, SmithKline Beecham Pharmaceuticals, Collegeville, PA, USA.
Abstract
AIM: Rosiglitazone is the most potent of the thiazolidinediones, a novel class of oral antidiabetic agents that reduce blood glucose levels by sensitizing peripheral tissues to insulin. This study was designed to identify doses of rosiglitazone that would lower fasting plasma glucose (FPG) in patients with type 2 diabetes. METHODS: In this 12-week, double-blind, multicentre study, 380 patients with FPG values > or =7.8 mmol/L (140 mg/dL) and < or =13.3 mmol/L (240 mg/dL) were randomly assigned to receive treatment 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 weeks of treatment. Secondary endpoints were changes in HbA1c, fructosamine, C peptide, insulin, lipid levels, and body weight (b.w.). Safety monitoring included clinical laboratory evaluations, electrocardiography, and echocardiography. 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 these 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 fatty 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 ratio or triglyceride levels in any rosiglitazone treatment group. Clinically insignificant dose-dependent increases in b.w. were observed in the rosiglitazone 1.0 and 2.0 mg b.i.d. treatment groups. CONCLUSIONS: Twelve weeks of treatment with rosiglitazone 2.0 mg b.i.d. significantly 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 rosiglitazone in patients with type 2 diabetes mellitus.
RCT Entities:
AIM: Rosiglitazone is the most potent of the thiazolidinediones, a novel class of oral antidiabetic agents that reduce blood glucose levels by sensitizing peripheral tissues to insulin. This study was designed to identify doses of rosiglitazone that would lower fasting plasma glucose (FPG) in patients with type 2 diabetes. METHODS: In this 12-week, double-blind, multicentre study, 380 patients with FPG values > or =7.8 mmol/L (140 mg/dL) and < or =13.3 mmol/L (240 mg/dL) were randomly assigned to receive treatment 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 weeks of treatment. Secondary endpoints were changes in HbA1c, fructosamine, C peptide, insulin, lipid levels, and body weight (b.w.). Safety monitoring included clinical laboratory evaluations, electrocardiography, and echocardiography. 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 these 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 fatty 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 ratio or triglyceride levels in any rosiglitazone treatment group. Clinically insignificant dose-dependent increases in b.w. were observed in the rosiglitazone 1.0 and 2.0 mg b.i.d. treatment groups. CONCLUSIONS: Twelve weeks of treatment with rosiglitazone 2.0 mg b.i.d. significantly 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 rosiglitazone in patients with type 2 diabetes mellitus.
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