Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes

OBJECTIVE- To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia. RESEARCH DESIGN AND METHODS- After a 4-week placebo run-in period, 959 pati ents were randomized to placebo or rosiglitazone (total daily dose 4 or 8 m g) for 26 weeks. The primary measure of efficacy was change in the HbA(1c) concentration. RESULTS- Rosiglitazone produced dosage-dependent reductions in HbA(1c) of 0 .8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b .i.d. groups, respectively, compared with placebo. Clinically significant d ecreases from baseline in HbA(1c) were observed in drug-naive patients at a ll rosiglitazone doses and in patients previously treated with oral monothe rapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decr eases from baseline in HbA(1c) were also observed with rosiglitazone 4 mg b .i.d. in patients previously treated with combination oral therapy. Approxi mately 33% of drug-naive patients treated with rosiglitazone achieved HbA(1 c) less than or equal to7% at study end. The proportions of patients with a t least one adverse event were comparable among the rosiglitazone and place bo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids i n all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related. CONCLUSIONS- Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well to lerated.