Low-dose rosiglitazone in patients with insulin-requiring type 2 diabetes

Background: The objective was to compare the efficacy and safety of adding low-dose rosiglitazone (2 or 4 mg/d) to insulin therapy vs continued insulin monotherapy in patients with type 2 diabetes mellitus who were unable to achieve glycemic control with insulin therapy alone. Methods: In this 24-week, double-blind study, 630 individuals with type 2 diabetes mellitus that was inadequately controlled with insulin therapy alone were randomized to treatment with rosiglitazone (2 or 4 mg/d) or placebo in combination with ongoing insulin therapy. The dosage of insulin therapy could be adjusted at the investigator's discretion if required for hypoglycemia or additional glycemic control. Results: The addition of rosiglitazone (2 or 4 mg/d) to insulin therapy significantly decreased mean glycated hemoglobin concentrations compared with placebo plus insulin (-0.3% [P=.02] and -0.4% [P <.001]) and compared with baseline (-0.6% and -0.8% [both P <.001]) after 24 weeks. The addition of 2 or 4 mg/d of rosiglitazone significantly decreased the C-reactive protein level (vs baseline: -22.0% [P <.001] and -34.2% [P <.001]; vs placebo: -22.2% [P=.003] and -32.0% [P <.001]) and fibrinogen (vs baseline: -10.5% and -12.0% [both P <.001]; vs placebo: -7.9% [P=.002] and -7.6% [P=.004]), while 4 mg/d of rosiglitazone significantly reduced matrix metalloproteinase 9 levels (vs baseline: -17.1%[P=.007]; vs placebo: -23.3% [P <.001]). The adverse event profile, including incidence of hypoglycemia and edema, was similar between treatment groups, and most adverse events were mild to moderate in intensity. Conclusions: The addition of low-dose rosiglitazone to insulin therapy is an effective and well-tolerated treatment option for patients with type 2 diabetes mellitus who continue to have poor glycemic control despite administration of exogenous insulin as monotherapy.