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

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.

• Authors: S Rosenblatt, B Miskin, N B Glazer, M J Prince, K E Robertson, Pioglitazone 026 Study Group
• Journal: Coronary artery disease (Coron Artery Dis) Vol. 12 Issue 5 Pg. 413-23 (Aug 2001) ISSN: 0954-6928 [Print] England
• PMID: 11491207 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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