Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial.
BACKGROUND
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.


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


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


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


METHODS
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] microIU/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] mm(2); 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. JAMA. 2000;284:472-477
Hadigan
C
C
Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, MA 02114, USA.
Corcoran
C
C
Basgoz
N
N
Davis
B
B
Sax
P
P
Grinspoon
S
S
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications*; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin