Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with Type II diabetes

Aims/hypothesis. The short-term efficacy, safety and tolerability of rosigl itazone were compared with placebo in patients with Type II (non-insulin-de pendent) diabetes mellitus in a dose-ranging study. Methods. After a 2-week placebo run-in phase, 303 patients were randomly as signed to 8 weeks of treatment with twice-daily placebo or 2, 4 or 6 mg of rosiglitazone. Results. All rosiglitazone doses significantly reduced fasting plasma gluco se compared with baseline. All rosiglitazone treatment groups showed signif icantly reduced peak postprandial glucose concentrations compared with base line (p < 0.001) and with placebo (p < 0.0001) and reduced postprandial glu cose excursion, without an increase in the area under the postprandial insu lin concentration-time curve. Rosiglitazone at 4 and 6 mg twice daily preve nted the increase in HbA(1c) observed in the placebo group. C peptide and s erum insulin concentrations were significantly reduced from baseline in all rosiglitazone treatment groups. In all rosiglitazone treatment groups, non esterified fatty acids decreased significantly (p < 0.0001) and triglycerid es did not change. Although total LDL and HDL cholesterol increased signifi cantly in the rosiglitazone treatment groups, total cholesterol/HDL ratios did not change significantly. The proportion of patients with one or more a dverse event was similar in all four treatment groups. No patient showed ev idence of hepatotoxicity. Conclusion/interpretation. Rosiglitazone given twice daily significantly re duced fasting and postprandial glucose concentrations, C peptide, insulin a nd nonesterified fatty acids in Type II diabetic patients. The glucose-lowe ring effect of the 4-mg twice-daily dose of rosiglitazone was similar to th at of 6-mg twice daily, suggesting that 4 mg twice daily should be the maxi mum clinical dose.