Document Detail

Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial.
MedLine Citation:
PMID:  15562376     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Several clinical studies have demonstrated that body weight increases after treatment with thiazolidinediones (TZDs). Prior studies have demonstrated an increase in insulin-stimulated lipid storage in adipose tissue. Some, but not all, studies demonstrate reductions in visceral adipose tissue. Changes in body weight are the result of changes in energy intake, energy expenditure, or both. OBJECTIVES: Based on these findings, the primary aim of this study was to evaluate the effect of TZDs on visceral, subcutaneous, and total body fat. Secondary aims were to determine the effects of pioglitazone on (a) energy expenditure, (b) hunger and satiety, (c) blood lipids, and (d) the role of insulinemia/sulfonylurea usage on weight gain in patients with type 2 diabetes. SUBJECTS AND METHODS: We performed a randomized, double-blind, placebo-controlled trial in 48 men and women with type 2 diabetes who had not previously received treatment with TZDs. Patients were treated for 24 weeks with 45 mg/d of pioglitazone or a matching placebo. Body composition was measured by dual-energy x-ray absorptiometry. Visceral and subcutaneous fat were measured by computed tomography. Resting metabolic rate and thermogenic response to a test meal were measured by indirect calorimetry before and after a standardized meal. Hunger and satiety were measured with visual analog scales before and after the same test meal. Blood was collected for the measurement of fasting glucose and insulin levels, hemoglobin A 1c levels, and lipid content. RESULTS: Pioglitazone treatment resulted in a decrease in hemoglobin A(1c) level by 0.96 +/- 1.1% vs 0.11 +/- 0.8% in the placebo group (P < .005). Body weight and fat increased steadily in the patients treated with pioglitazone during the 6 months of the study (+3.9 +/- 3.1 kg at 6 months in pioglitazone-treated patients vs -0.8 +/- 3.4 kg in the placebo-treated patients). Subcutaneous fat in the trunk, arms, and legs were all increased in the pioglitazone-treated group. Visceral fat did not change significantly in either group. Neither resting metabolic rate nor the thermogenic responses to a meal were altered by pioglitazone. Subjective measures of hunger (visual analog scale) did not change with pioglitazone treatment. Triglycerides fell in the pioglitazone-treated group (-58.5 +/- 124 mg/dL, P < .003). Neither the prior use of sulfonylureas nor the level of insulinemia before treatment was a predictor of weight or fat change. CONCLUSION: Pioglitazone increased subcutaneous body fat, but not visceral fat. There was no measurable effect on energy expenditure or hunger/satiety. In contrast to the placebo-treated patient with diabetes, weight gain occurs in the face of falling hemoglobin A(1c) and triglyceride levels.
Steven R Smith; Lilian De Jonge; Julia Volaufova; Yinmei Li; Hui Xie; George A Bray
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  54     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-11-24     Completed Date:  2005-02-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24-32     Citation Subset:  IM    
Department of Molecular Endocrinology, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
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MeSH Terms
Body Composition / drug effects*
Body Weight / drug effects
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism
Double-Blind Method
Energy Metabolism / drug effects*
Hunger / drug effects
Hypoglycemic Agents / therapeutic use*
Lipid Metabolism
Liver / metabolism
Middle Aged
Pain Measurement
Thiazolidinediones / pharmacology,  therapeutic use*
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Thiazolidinediones; 111025-46-8/pioglitazone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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