A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus

doi:10.1016/S0149-2918(03)80068-1

Clinical Therapeutics

Volume 25, Issue 4, April 2003, Pages 1074-1095

https://doi.org/10.1016/S0149-2918(03)80068-1 Get rights and content

Abstract

Objective: The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA_1c), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia.

Methods: Patients with type 2 diabetes mellitus (HbA_1c ≥6.5% and ≤9.8%) who had not previously received insulin or oral antihyperglycemic medications (OAMs) were randomized to treatment with placebo, pioglitazone 30 mg QD, or pioglitazone 45 mg QD in double-blind fashion for 16 weeks at 41 centers in Canada and Spain.

Results: A total of 297 patients were randomized (99 in each group). Overall, 286 (96.3%) were white. Mean (SD) age was 58.4 (10.9) years (range, 24–85 years), mean (SD) body mass index was 31.4 (4.8) kg/m², mean (SD) duration of type 2 diabetes mellitus was 20.0 (37.4) months, and 30.6% of patients were receiving medication for dyslipidemia. Treatment with pioglitazone 30 or 45 mg QD for 16 weeks reduced mean HbA_1c by 0.8% and 0.9% from baseline, respectively (both P < 0.001 vs baseline and placebo). A reduction in HbA_1c of 0.2% was observed in the placebo group (P = 0.025). In patients with medium (≥7% to <8%) or high (≥8% to ≤9.8%) baseline HbA_1c, both doses of pioglitazone significantly reduced HbA_1c (both P < 0.001 vs plcebo). Pioglitazone 30 and 45 mg significantly reduced fasting serum insulin versus placebo (P = 0.008 and P = 0.006, respectively) and increased insulin sensitivity by Homeostasis Model Assessment versus placebo (P = 0.039 and P = 0.001, respectively). Relative to placebo, pioglitazone 30 and 45 mg significantly increased high-density lipoprotein cholesterol (HDL-C [P = 0.028 and P < 0.001, respectively]) and lowered the atherogenic index of plasma (P = 0.018 and P < 0.001, respectively). Pioglitazone 45 mg also significantly reduced serum triglycerides, apolipoprotein B, and total cholesterol:HDL-C ratio versus placebo (P = 0.007, P = 0.015, and P = 0.005, respectively). Pioglitazone 30 and 45 mg were associated with a significant reduction in serum alanine aminotransferase relative to placebo (P = 0.036 and P = 0.005, respectively). Pioglitazone appeared to be safe and was well tolerated.

Conclusions: In the present study, pioglitazone 30 and 45 mg produced significant improvements in HbA_1c, insulin sensitivity, and lipid profile in OAM-naive patients with type 2 diabetes mellitus with suboptimal glycemic control and mild dyslipidemia.

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^☆: This work was presented in part at the 62nd Annual Meeting and Scientific Sessions of the American Diabetes Association, June 14–18, 2002, Sna Francisco, California (published as abstracts in Diabetes. 2002; 51[Suppl 2]: 414P, 1976PO, 2042PO); and at the Canadian Diabetes Association Meeting, October 3–5, 2002, Vancouver, Canada (published as an abstract in Can J Diabetes. 2002;26[Suppl 1]:A222).

^∗: Members of the GLAB Study Group are listed in the Acknowledgements.

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Original researchA randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus☆

Abstract

Lancet

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study

Diabetes Res Clin Pract

Diabetes and coronary artery disease

Diabetes Spectrum

Management of dyslipidemia in adults with diabetes

Diabetes Care

Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: The Propective Study

Diabetologia

Insulin resistance and its consequences: Type 2 diabetes mellitus and coronary heart disease

Peroxisome proliferator-activated receptor agonists, hyperlipidaemia, and atherosclerosis

Pharmacol Ther

Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: A randomized, placebo-controlled study

Am J Med

Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone

Diabetes Care

Efficacy and safety of pioglitazone in type 2 diabetes: A randomised, placebo-controlled study in patients receiving stable insulin therapy

Int J Clin Pract

The plasma parameter log (TG/HDL-C) as an atherogenic index: Correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL))

Clin Biochem

Pioglitazone reduces atherogenic index of plasma, an indirect indicator of LDL particle size

Diabetes

Standards of medical care for patients with diabetes mellitus

Diabetes Care

Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: A 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group

Diabetes Care

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

Coron Artery Dis

N Engl J Med

Correct homeostasis model assessment (HOMA) evaluation uses the computer program

Diabetes Care

A sharper Bonferroni procedure for multiple significance testing

Biometrika

Dose-response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes

Diabetes Care

Insulin sensitivity and its measurement: Structural commonalities among the methods

J Clin Endocrinol Metab

Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: Studies in subjects with various degress of glucose tolerance and insulin sensitivity

Diabetes Care

Original research
A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus☆