Comparison of Rosiglitazone and Metformin for Treating HIV Lipodystrophy

A Randomized Trial

6 September 2005 | Volume 143 Issue 5 | Pages 337-346

Background: The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and cardiovascular risk factors.

Objective: To compare the effects of the peroxisome proliferator–activated receptor- agonist rosiglitazone and metformin for treating HIV lipodystrophy.

Design: An open, randomized, 6-month clinical trial.

Setting: University Medical Center, Utrecht, the Netherlands.

Patients: 39 HIV-infected men with lipodystrophy.

Intervention: Rosiglitazone, 8 mg/d, or metformin, 2 g/d.

Measurements: Insulin sensitivity estimated by the oral glucose tolerance test, subcutaneous and visceral abdominal fat measured by single-slice computed tomography, endothelial function measured by flow-mediated vasodilation, and fasting plasma measurements. Two patients in the metformin group withdrew from the study. Complete case analysis was performed.

Results: Compared with metformin, rosiglitazone increased subcutaneous abdominal fat (between-treatment change from baseline, 27 cm² [95% CI, 7 cm² to 46 cm²]) and visceral abdominal fat (between-treatment change from baseline, 24 cm² [CI, 6 cm² to 51 cm²]). The area under the curve for insulin after the oral glucose tolerance test decreased similarly with both agents, but only rosiglitazone increased adiponectin levels. Metformin showed greater benefits on fasting lipid profile than rosiglitazone. Flow-mediated vasodilation statistically significantly increased with metformin (mean change, 1.5% [CI, 0.4% to 3.3%]) and not with rosiglitazone (mean change, 0.7% [CI, –1.1% to 2.7%]). The metformin versus rosiglitazone increases did not statistically differ. Rosiglitazone and metformin did not change C-reactive protein levels.

Limitations: This small trial was not blinded or placebo-controlled and did not measure clinical outcomes.

Conclusions: The findings emphasize the importance of individualized care in HIV-infected patients. Although rosiglitazone may partly correct lipoatrophy, metformin improves visceral fat accumulation, fasting lipid profile, and endothelial function.

Editors' Notes Context Antiretroviral therapy sometimes causes peripheral fat loss and central fat accumulation (lipodystrophy) and increases metabolic risk factors in patients with HIV. Contribution The investigators randomly assigned 39 HIV-infected men with lipodystrophy to rosiglitazone or metformin for 6 months. Compared with metformin, rosiglitazone increased abdominal fat and adiponectin levels. Compared with rosiglitazone, metformin reduced fasting lipid levels and improved some measures of brachial artery vasodilation. Both agents decreased glucose and insulin levels similarly. Cautions This open-label trial was small and did not assess clinical outcomes. Implications Available evidence does not establish whether rosiglitazone or metformin better benefits HIV-infected patients with lipodystrophy. –The Editors

 

Author and Article Information

From University Medical Center, Utrecht, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands; St. Franciscus Gasthuis, Rotterdam, the Netherlands; and Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Reus, Spain.

Trial ISRCTN36766542

Acknowledgments: The authors thank Dr. E.P. Martens (Centre for Biostatistics, University of Utrecht, Utrecht, the Netherlands) for his help with the statistical analysis and Dr. R. van de Geest (Leiden University Medical Center, Leiden, the Netherlands) for his help with the reading and analysis of the computed tomography images.

Grant Support: By an unrestricted grant from GlaxoSmithKline. Dr. van Wijk has received educational grant support from the Dutch Organization for Scientific Research, and Dr. de Koning is recipient of a Career Development Grant from the Dutch Diabetes Research Foundation.

Potential Financial Conflicts of Interest: Grants received: J.P.H. van Wijk (Dutch Organization for Scientific Research), E.J.P. de Koning (Dutch Diabetes Research Foundation).

Requests for Single Reprints: Jeroen P.H. van Wijk, MD, Departments of Infectious Disease and Internal Medicine, University Medical Center, Room G02.402, PO Box 85500, 3508 GA Utrecht, the Netherlands; e-mail, j.p.h.vanwijk{at}azu.nl.

Current Author Addresses: Drs. van Wijk and Hoepelman: Departments of Infectious Disease and Internal Medicine, University Medical Center, Room G02.402, PO Box 85500, 3508 GA Utrecht, the Netherlands.

Drs. de Koning and Rabelink and Mr. op't Roodt: Departments of Nephrology, Leiden University Medical Center, Room C3-P, PO Box 9600, 2300 RC Leiden, the Netherlands.

Dr. Castro Cabezas: Departments of Internal Medicine, St. Franciscus Gasthuis, PO Box 10900, 3004 BA Rotterdam, the Netherlands.

Dr. Joven: Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain.

Author Contributions: Conception and design: J.P.H. van Wijk, E.J.P. de Koning, M. Castro Cabezas, T.J. Rabelink, A.I. Hoepelman.

Analysis and interpretation of the data: J.P.H. van Wijk, E.J.P. de Koning, M. Castro Cabezas, J. op't Roodt, J. Joven, T.J. Rabelink.

Drafting of the article: J.P.H. van Wijk, E.J.P. de Koning, M. Castro Cabezas, J. Joven, T.J. Rabelink, A.I. Hoepelman.

Critical revision of the article for important intellectual content: J.P.H. van Wijk, E.J.P. de Koning, M. Castro Cabezas, J. op't Roodt, T.J. Rabelink.

Final approval of the article: J.P.H. van Wijk, E.J.P. de Koning, M. Castro Cabezas, J. op't Roodt, J. Joven, T.J. Rabelink, A.I. Hoepelman.

Provision of study materials or patients: J.P.H. van Wijk, J. op't Roodt, A.I. Hoepelman.

Statistical expertise: J.P.H. van Wijk, J. Joven, A.I. Hoepelman.

Obtaining of funding: J.P.H. van Wijk, E.J.P. de Koning, M. Castro Cabezas, T.J. Rabelink, A.I. Hoepelman.

Administrative, technical, or logistic support: J.P.H. van Wijk, J. op't Roodt, J. Joven, A.I. Hoepelman.

Collection and assembly of data: J.P.H. van Wijk, A.I. Hoepelman.