Long-term safety of pioglitazone versus glyburide in patients with recently diagnosed type 2 diabetes mellitus

Pharmacotherapy. 2006 Oct;26(10):1388-95. doi: 10.1592/phco.26.10.1388.


Study objective: To evaluate the long-term safety and efficacy of glyburide versus pioglitazone in patients with a recent diagnosis of type 2 diabetes mellitus.

Design: Prospective, randomized, multicenter, double-blind trial with a 16-week titration period and a 40-week maintenance period.

Setting: Sixty-five investigative sites in the United States and Puerto Rico.

Patients: Five hundred two subjects with a recent diagnosis of type 2 diabetes that was unsuccessfully treated with diet and exercise were randomly assigned to study treatment. Of the 251 patients in each treatment group, 128 (51.0%) glyburide-treated patients and 134 (53.4%) pioglitazone-treated patients completed the study.

Interventions: Dosages of randomly assigned glyburide and pioglitazone were titrated every 4 weeks for 16 weeks in 5-mg/day and 15-mg/day increments, respectively, until a fasting plasma glucose level between 69 and 141 mg/dl was achieved. The optimized regimen was maintained during the subsequent 40-week double-blind phase.

Measurements and main results: At week 56, glyburide and pioglitazone improved glucose control comparably (change in hemoglobin A(1c) -2.02% and -2.07%, respectively, p=0.669). Withdrawal due to lack of efficacy or adverse events occurred more frequently with glyburide (20.8%) than pioglitazone (12.8%, p<0.032). Significantly higher percentages of glyburide- than pioglitazone-treated patients had a hypoglycemic (24.3% vs 4.4%, p=0.0001) or cardiac (8.8% vs 4.4%, p=0.0478) event. Edema (4.8% vs 7.9%, p=0.1443) and weight gain (4.4% vs 4.0%, p=0.8238) did not differ significantly between the glyburide and pioglitazone groups. Only a few patients discontinued study drug because of weight gain (one glyburide, one pioglitazone), edema (one pioglitazone), or a cardiac event (two glyburide).

Conclusion: With long-term treatment, both glyburide and pioglitazone resulted in comparable glycemic control; however, pioglitazone was associated with less hypoglycemia and fewer withdrawals due to lack of efficacy or adverse events.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Glyburide / adverse effects*
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Pioglitazone
  • Risk Assessment
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use
  • Time Factors


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Glyburide
  • Pioglitazone