Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus:: a 42-month, open-label, observational, primary label, care study

Background: Insulin resistance and declining beta-cell function are the core defects in type 2 diabetes mellitus. It has been suggested that deteriorating glycemic control is related to baseline hemoglobin A(1c) ( HbA(1c)) values and remaining beta-cell function. Patients and methods: We report glycemic data from a 3.5-year, open-label, observational, primary care study comparing 30 mg/day pioglitazone with 3.5 mg/day glibenclamide add-on to stable metformin monotherapy in 500 patients with type 2 diabetes diabetes. Insulin commencement was. considered for patients with HbA(1c) >= 8.0% or when vascular complications occurred. The change in HbA(1c) compared with baseline and the difference in time to failure to maintain glycemic control were calculated. Results: At endpoint, HbA(1c) had decreased by 1.0% in the pioglitazone group ( p < 0.005) and by 0.6% in the glibenclamide group ( p < 0.05). Annual progression rates to insulin treatment were 6.6% ( pioglitazone) and 16.4% ( glibenclamide glibenclamide; p < 0.001 between-group difference). Mean weight increases of 3.5 +/- 0.42 kg in the pioglitazone group and 3.3 +/- 0.38 kg in the glibenclamide group were noted. Overall, both treatments were well tolerated. Conclusions: Pioglitazone add-on to metformin revealed significant benefits in long-term glycemic control compared with glibenclamide. This difference may be explained by a large between-group difference in HOMA-S, which was shown group to correlate significantly to the change in HbA(1c). This suggests that a strategy to reduce insulin resistance to lower the burden of the beta-cell is superior to treatment with glibenclamide.