The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus

Coron Artery Dis. 2001 Aug;12(5):413-23. doi: 10.1097/00019501-200108000-00011.

Abstract

Background: To evaluate the glycemic control, lipid effects, and safety of pioglitazone in patients with type 2 diabetes mellitus.

Design and methods: Patients (n = 197) with type 2 diabetes mellitus, a hemoglobin A1c (HbA1c) > or = 8.0%, fasting plasma glucose (FPG) > 7.7 mmol/l (140 mg/dl), and C-peptide > 0.331 nmol/l (1 ng/ml) were enrolled in this 23-week multi-center (27 sites), double-blind clinical trial and randomized to receive either a placebo or pioglitazone HCl 30 mg (pioglitazone), administered once daily, as monotherapy. Patients were required to discontinue all anti-diabetic medications 6 weeks before receiving study treatment. Efficacy parameters included HbA1c fasting plasma glucose (FPG), serum C-peptide, insulin, triglycerides (Tg), and cholesterol (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C]). Adverse event rates, serum chemistry, and physical examinations were recorded.

Results: Compared with placebo, pioglitazone significantly (P= 0.0001) reduced HbA1c (-1.37% points), FPG (-3.19 mmol/l; -57.5 mg/dl), fasting C-peptide (-0.076+/-0.022 nmol/l), and fasting insulin (-11.88+/-4.70 pmol/l). Pioglitazone significantly (P < 0.001) decreased insulin resistance (HOMA-IR; -12.4+/-7.46%) and improved beta-cell function (Homeostasis Model Assessment (HOMA-BCF); +47.7+/-11.58%). Compared with placebo, fasting serum Tg concentrations decreased (-16.6%; P = 0.0178) and HDL-C concentrations increased (+12.6%; P= 0.0065) with pioglitazone as monotherapy. Total cholesterol and LDL-C changes were not different from placebo. The overall adverse event profile of pioglitazone was similar to that of placebo, with no evidence of drug-induced elevations of serum alanine transaminase (ALT) concentrations or hepatotoxicity.

Conclusions: Pioglitazone improved insulin resistance and glycemic control, as well as Tg and HDL-C - which suggests that pioglitazone may reduce cardiovascular risk for patients with type 2 diabetes.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Arteriosclerosis / etiology
  • Blood Glucose / analysis
  • Blood Glucose / drug effects*
  • C-Peptide / blood
  • C-Peptide / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / analysis
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hyperlipidemias / blood
  • Hyperlipidemias / complications*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin Resistance / physiology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology
  • Lipids / blood
  • Lipoproteins / blood
  • Lipoproteins / drug effects
  • Male
  • Middle Aged
  • Pioglitazone
  • Single-Blind Method
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*
  • Thiazolidinediones*
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Lipoproteins
  • Thiazoles
  • Thiazolidinediones
  • Pioglitazone