A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes

OBJECTIVE- To determine the efficacy and safety of rosiglitazone (RSG) when added to insulin in the treatment of type 2 diabetic patients who are inadequately controlled on insulin monotherapy. RESEARCH DESIGN AND METHODS- After 8 weeks of insulin standardization and placebo (PBO) run-in, 319 type 2 diabetic patients with mean baseline HbA_1c ≥ 7.5% (8.9 ± 1.1 to 9.1 ± 1.3) on twice-daily insulin therapy (total daily dose ≥30 U) were randomized to 26 weeks of additional treatment with RSG (4 or 8 mg daily) or PBO. Insulin dose could be downtitrated only for safety reasons. The primary end point was reduction of HbA_1c from baseline. RESULTS- RSG 4 and 8 mg daily significantly improved glycemic control, which was unchanged on PBO. By intent-to-treat analysis, treatment with RSG 8 mg plus insulin resulted in a mean reduction from baseline in HbA_1c of 1.2% (P < 0.0001), despite a 12% mean reduction of insulin dosage. Over 50% of subjects treated daily with RSG 8 mg plus insulin had a reduction of HbA_1c ≥ 1.0%. Neither total:HDL cholesterol nor LDL:HDL cholesterol ratios significantly changed with RSG treatment. Serious adverse events did not differ among groups. CONCLUSIONS- The addition of RSG to insulin treatment results in significant improvement in glycemic control and is generally well tolerated.