Improved Triglycerides and Insulin Sensitivity with 3 Months of Acipimox in Human Immunodeficiency Virus-infected Patients with Hypertriglyceridemia

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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.

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