Glycemic Control and Treatment Failure With Pioglitazone Versus Glibenclamide in Type 2 Diabetes Mellitus: A 42-month, Open-Label, Observational, Primary Care Study

Curr Med Res Opin. 2006 Jun;22(6):1211-5. doi: 10.1185/030079906X112598.


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. Insulin commencement was considered for patients with HbA(1c) > or = 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; 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 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glyburide / administration & dosage*
  • Glycated Hemoglobin A / analysis*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Metformin / administration & dosage
  • Middle Aged
  • Pioglitazone
  • Primary Health Care
  • Prospective Studies
  • Thiazolidinediones / administration & dosage*
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Metformin
  • Glyburide
  • Pioglitazone