This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (159)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • HIV/AIDS  • Randomized Controlled Trial  • Alert me on articles by topic

A Randomized Controlled Trial

Colleen Hadigan, MD; Colleen Corcoran, NP; Nesli Basgoz, MD; Benjamin Davis, MD; Paul Sax, MD; Steven Grinspoon, MD

JAMA. 2000;284:472-477.

Context  A syndrome of lipodystrophy, characterized by fat redistribution and insulin resistance, has been estimated to affect the majority of human immunodeficiency virus (HIV)–infected individuals who are treated with combination antiretroviral therapy. There are no proven therapies for the metabolic disturbances associated with HIV lipodystrophy syndrome.

Objective  To determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis.

Design and Setting  Randomized, double-blind, placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000.

Patients  Twenty-six HIV-infected, nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test (OGTT) results, hyperinsulinemia, or both.

Interventions  Patients were randomly assigned to receive metformin, 500 mg twice daily (n = 14), or identical placebo (n = 12), for 3 months.

Main Outcome Measures  Insulin area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at baseline vs at 3-month follow-up and compared between treatment groups.

Results  Patients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (-2930 [912] vs -414 [432] µIU/mL [-20349 {6334} vs -2875 {3000} pmol/L]; P = .01), weight (-1.3 [0.6] vs 1.1 [0.4] kg; P = .005), and diastolic blood pressure (-5 [4] vs 5 [2] mm Hg; P = .009) vs controls, respectively. Metformin therapy was associated with a decrease in visceral abdominal fat (VAT; -1115 [819] vs 1191 [699] mm²; P = .08) and a proportional reduction in subcutaneous abdominal fat (SAT); the VAT-SAT ratio was unchanged in metformin-treated vs placebo-treated patients. No increase in lactate or liver transaminase levels was observed with metformin treatment. Mild diarrhea was the most common adverse effect of metformin. No patient discontinued therapy because of adverse effects.

Conclusions  This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy.

Author Affiliations: Neuroendocrine Unit (Drs Hadigan and Grinspoon and Ms Corcoran) and Infectious Disease Unit (Drs Basgoz and Davis), Massachusetts General Hospital, and the Combined Program in Pediatric Gastroenterology and Nutrition (Dr Hadigan) and Division of Infectious Diseases, Brigham and Women's Hospital (Dr Sax), Harvard Medical School, Boston.

RELATED ARTICLE

July 26, 2000
JAMA. 2000;284(4):505-506.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options
Mallewa et al.
J Antimicrob Chemother 2008;62:648-660.
ABSTRACT | FULL TEXT  

A 39-Year-Old Man With HIV-Associated Lipodystrophy
Fuller
JAMA 2008;300:1056-1066.
ABSTRACT | FULL TEXT  

Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation: A Randomized Controlled Trial
Lo et al.
JAMA 2008;300:509-519.
ABSTRACT | FULL TEXT  

State of the Science Conference: Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS: Executive Summary
Grinspoon et al.
Circulation 2008;118:198-210.
FULL TEXT  

Prevention Strategies for Cardiovascular Disease in HIV-Infected Patients
Stein et al.
Circulation 2008;118:e54-e60.
FULL TEXT  

Review: Clinical aspects of the management of HIV lipodystrophy
Wierzbicki et al.
British Journal of Diabetes & Vascular Disease 2008;8:113-119.
ABSTRACT  

Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection
Samaras
J Antimicrob Chemother 2008;61:238-245.
ABSTRACT | FULL TEXT  

Metabolic Effects of a Growth Hormone-Releasing Factor in Patients with HIV
Falutz et al.
NEJM 2007;357:2359-2370.
ABSTRACT | FULL TEXT  

HIV and HIV treatment: effects on fats, glucose and lipids
Gkrania-Klotsas and Klotsas
Br Med Bull 2007;84:49-68.
ABSTRACT | FULL TEXT  

Effects of High-Intensity Endurance and Resistance Exercise on HIV Metabolic Abnormalities: A Pilot Study
Robinson et al.
Biol Res Nurs 2007;8:177-185.
ABSTRACT  

Metabolic and skeletal complications of HIV infection: the price of success.
Morse and Kovacs
JAMA 2006;296:844-854.
ABSTRACT | FULL TEXT  

Aspects of type 2 diabetes and related insulin-resistant States.
Bloomgarden
Diabetes Care 2006;29:732-740.
FULL TEXT  

Comparison of Rosiglitazone and Metformin for Treating HIV Lipodystrophy: A Randomized Trial
van Wijk et al.
ANN INTERN MED 2005;143:337-346.
ABSTRACT | FULL TEXT  

Adverse Effects Associated With Antiretroviral Therapy and Potential Management Strategies
Rudorf and Krikorian
Journal of Pharmacy Practice 2005;18:258-277.
ABSTRACT  

Current perspectives on HIV-associated lipodystrophy syndrome
Milinkovic and Martinez
J Antimicrob Chemother 2005;56:6-9.
ABSTRACT | FULL TEXT  

Therapeutic approaches to combating lipoatrophy: do they work?
Martin and Mallon
J Antimicrob Chemother 2005;55:612-615.
ABSTRACT | FULL TEXT  

Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults
Grinspoon and Carr
NEJM 2005;352:48-62.
FULL TEXT  

Growth Hormone-Releasing Hormone in HIV-Infected Men With Lipodystrophy: A Randomized Controlled Trial
Koutkia et al.
JAMA 2004;292:210-218.
ABSTRACT | FULL TEXT  

Metabolic Effects of Rosiglitazone in HIV Lipodystrophy: A Randomized, Controlled Trial
Hadigan et al.
ANN INTERN MED 2004;140:786-794.
ABSTRACT | FULL TEXT  

Pharmacologic Therapy for HIV-Associated Lipodystrophy
Benavides and Nahata
The Annals of Pharmacotherapy 2004;38:448-457.
ABSTRACT | FULL TEXT  

Altered Glucose Metabolism in HIV-infected Patients Treated With HAART
Lee
Journal of Pharmacy Practice 2004;17:80-86.
ABSTRACT  

Human Immunodeficiency Virus/Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome: Clinical Presentation, Pathophysiology, and Therapeutic Strategies
Leow et al.
J. Clin. Endocrinol. Metab. 2003;88:1961-1976.
FULL TEXT  

Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy
Luzi et al.
Am. J. Physiol. Endocrinol. Metab. 2003;284:E274-E280.
ABSTRACT | FULL TEXT  

Thiazolidinediones Could Improve Endothelial Dysfunction and Risk of Premature Coronary Heart Disease in HIV-Infected Patients
Carrillo-Jimenez et al.
J CARDIOVASC PHARMACOL THER 2002;7:207-210.
ABSTRACT  

Insulin Resistance and HIV-Related Lipoatrophy
Mikhail et al.
JAMA 2002;288:1716-1716.
FULL TEXT  

Sustained Benefits of Metformin Therapy on Markers of Cardiovascular Risk in Human Immunodeficiency Virus-Infected Patients with Fat Redistribution and Insulin Resistance
Hadigan et al.
J. Clin. Endocrinol. Metab. 2002;87:4611-4615.
ABSTRACT | FULL TEXT  

Guidelines for Using Antiretroviral Agents among HIV-Infected Adults and Adolescents: The Panel on Clinical Practices for Treatment of HIV
Dybul et al.
ANN INTERN MED 2002;137:381-433.
ABSTRACT | FULL TEXT  

Impaired glucose tolerance and metformin: clinical and mechanistic aspects
Hermann and Wiernsperger
British Journal of Diabetes & Vascular Disease 2002;2:177-183.
ABSTRACT  

Drug-Induced Hyperglycemia
Luna and Feinglos
JAMA 2001;286:1945-1948.
FULL TEXT  

Editorial: The Rational Use of Growth Hormone in HIV-Infected Patients
Grinspoon and Gelato
J. Clin. Endocrinol. Metab. 2001;86:3478-3479.
FULL TEXT  

The Effects of Recombinant Human Growth Hormone on Body Composition and Glucose Metabolism in HIV-Infected Patients with Fat Accumulation
Lo et al.
J. Clin. Endocrinol. Metab. 2001;86:3480-3487.
ABSTRACT | FULL TEXT  

Metformin Is an Effective Therapy for the HIV Lipodystrophy Syndrome
Journal Watch Dermatology 2000;2000:4-4.
FULL TEXT  

HIV Lipodystrophy Syndrome: A Novel Approach to Treatment
JWatch Infect. Diseases 2000;2000:3-3.
FULL TEXT