Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome

Background: Treatment with thiazolidinediones (TZDs) produces weight gain. Objective: To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM). Design: This 16‐week randomized, open‐label, parallel arm study compared three groups: (i) pioglitazone plus the American Diabetes Association diet (Pio + ADA); (ii) pioglitazone plus a portion control weight loss diet (Pio + PC); (iii) metformin plus the American Diabetes Association diet (Met + ADA). All participants received the same advice about calorie reduction, lifestyle change and exercise. Methods: Fifty‐one men and women with T2DM, naive to TZDs, were randomized to a 16‐week study. Pioglitazone (Pio) was titrated to a dose of 45 mg/day and metformin (Met) to a dose of 2 g/day. Fasting blood was collected for lipids, insulin and glycosylated haemoglobin A1c (HbA1c) at baseline and 16 weeks. Results: Forty‐eight of fifty‐one randomized subjects completed the study. Patients treated with Pio + ADA gained 2.15 ± 1.09 kg (mean ± SD) compared with a weight loss of 2.59 ± 1.25 kg (p < 0.05) in the Pio + PC group, and a weight loss of 3.21 ± 0.7 kg (p < 0.05) in the Met + ADA group. Waist circumference and visceral adipose tissue decreased significantly more in the Pio + PC group than in the Pio + ADA group. High‐density lipoprotein cholesterol levels were significantly increased in the Pio + PC group compared with the Met + ADA group. Pioglitazone reduced insulin resistance (homeostasis model assessment of insulin resistance (HOMA‐IR)) more than metformin. No significant differences between groups were seen for glucose, insulin, HbA1c or low‐density lipoprotein cholesterol levels. Conclusions: Pio + PC, prevented weight gain, reduced waist circumference and visceral fat compared with Pio + ADA diet.