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

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 (HbAlc), 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 (HbAlc >6.5% and <9.8%) who had not previously received insulin or oral antihyperglycemic medications (OAMs) were randomized to treatment with placebo, piogfitazone 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/m 2, 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 HbAlc by 0.8% and 0.9% from baseline, respectively (both P < 0.001 vs baseline and placebo). A reduction in HbAlc 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 HbAlc, both doses of pioglitazone significantly reduced HbAlc (both P < 0.001 vs placebo). 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 HbAlc, insulin sensitivity, and lipid profile in OAMnaive patients with type 2 diabetes mellitus with suboptimal glycemic control and mild dyslipidemia. (Clin Ther.

Pioglitazone elicits long-term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide-based regimens

“…In addition, PIO-based regimens significantly reduced fasting serum insulin levels, C-peptide levels, and 32-33 split pro-insulin levels over the 52-week time course, while GLIC-based regimens were associated with net increases in each of these measures [5]. These data are consistent with previous studies investigating the effects of PIO monotherapy on insulin sensitivity [19,20], and highlight an important difference between the mechanisms of action of PIO (increasing insulin sensitivity) and GLIC (increasing insulin secretion). This distinction may be important in the long-term care of patients with type 2 diabetes given the association of insulin resistance with the development of cardiovascular complications in this population [8][9][10][11].…”

Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes

“…These studies have also reported that pioglitazone modulates carbohydrate and lipid metabolism, increases insulin sensitivity, affects vasculature and may improve some of the risk factors associated with the metabolic syndrome [6][7][8][9][10][11][12][13][14][15].…”

“…Several clinical trials have demonstrated the short-term beneficial effects of pioglitazone on glycaemic control, both alone [6][7][8][9][10][11] and when added as a second agent in combination therapy [12][13][14][15]. These studies have also reported that pioglitazone modulates carbohydrate and lipid metabolism, increases insulin sensitivity, affects vasculature and may improve some of the risk factors associated with the metabolic syndrome [6][7][8][9][10][11][12][13][14][15].…”

Improvement of Glycemic Control, Triglycerides, and HDL Cholesterol Levels With Muraglitazar, a Dual (α/γ) Peroxisome Proliferator–Activated Receptor Activator, in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy

“…Edema has been reported in up to 16% of patients treated with thiazolidinedione monotherapy (9,12,(15)(16)(17)(18). Both muraglitazar and pioglitazone therapy were associated with edema (11.8 and 8.9%, respectively, at week 50) in the present study.…”