Improved triglycerides and insulin sensitivity with 3 months of acipimox in human immunodeficiency virus-infected patients with hypertriglyceridemia

Abstract

Context: Metabolic abnormalities such as hypertriglyceridemia remain a challenge for optimizing long-term health in HIV-infected patients.

Objective: Elevation of free fatty acids (FFAs) may contribute to hyperlipidemia and insulin resistance in HIV. We evaluated the efficacy and safety of chronic inhibition of lipolysis in HIV-infected men and women with hypertrigyceridemia. We hypothesized that acipimox would lead to significant reductions in triglycerides and improved insulin sensitivity, compared with placebo.

Design: A 3-month, randomized, double-blind, controlled trial of acipimox (250 mg thrice daily) vs. placebo was conducted in 23 HIV-infected men and women with hypertriglyceridemia (>150 mg/dl), abnormal fat distribution, and no current lipid-lowering therapy. The primary outcome variable was triglyceride concentration, and insulin sensitivity measured by hyperinsulinemic euglycemic clamp was a secondary outcome.

Setting: The study was conducted at an academic medical center.

Results: Acipimox resulted in significant reductions in FFAs [mean change -0.38 (0.06) vs. 0.08 (0.06) mEq/liter with placebo, -68 vs. +17% change from mean baseline, P < 0.0001], decreased rates of lipolysis (P < 0.0001), and a median triglyceride decrease from 238 mg/dl at baseline to 190 mg/dl, compared with an increase from 290 to 348 mg/dl in the placebo group (P = 0.01). Acipimox improved insulin sensitivity [acipimox +2.31 (0.74) vs. placebo -0.21 (0.90) mg glucose per kilogram lean body mass per minute, or +31 vs. -2% change from mean baseline values, P = 0.04]. Improvements in insulin sensitivity were significantly correlated with reductions in FFAs (r = -0.62, P = 0.003) and lipolysis (r = -0.59, P = 0.005).

Conclusions: Acipimox resulted in significant sustained reductions in lipolysis, improved glucose homeostasis, and significant but modest reductions in triglycerides in HIV-infected individuals with abnormal fat distribution and hypertriglyceridemia. Improvement in overall metabolic profile with acipimox suggests a potential clinical utility for this agent that requires further investigation.

Figures

Fig. 1

Median triglyceride concentration (with error bars representing IQR) over 3 months, acipimox (solid bars, n = 11) and placebo (white bars, n = 12), and repeated-measures ANOVA (P = 0.01) between the two groups.

Fig. 2

Baseline and 3-month FFA concentrations (A) and basal lipolysis (B) measured by Ra glycerol and Ra glycerol during hyperinsulinemic clamp (C) with placebo (open bars, n=10) and acipimox (solid bars, n=11). P values represent the results of t tests between groups at 3 months; there were no differences between groups at baseline.