Semaglutide Reduces Abdominal VAT in Patients With HIV-Related Lipohypertrophy

A recent phase 2b clinical trial evaluated semaglutide's efficacy in reducing abdominal visceral adipose tissue (VAT) in patients with HIV-associated lipohypertrophy, revealing significant adipose reductions. Participants treated with semaglutide experienced a 30.6% decrease in abdominal VAT compared with placebo. Given the persistent issue of lipohypertrophy in people with HIV, which is associated with elevated cardiometabolic risk and lacks effective treatments, these findings suggest potential therapeutic advancement.

HIV-associated lipohypertrophy, characterized by visceral fat accumulation, affects many people with HIV and contributes to cardiometabolic comorbidities. The researchers aimed to discover if the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, commonly used for diabetes management and obesity, could reduce adipose tissue in this population due to its metabolic effects.

This randomized, double-blind, placebo-controlled study enrolled 108 patients with HIV, a BMI ≥25 kg/m² and no diabetes, randomly assigning them to semaglutide (n = 54) or placebo (n = 54) for a 32-week period. Following an 8-week dose escalation, semaglutide was administered weekly at 1.0 mg for 24 weeks. Primary endpoints included changes in adipose tissue distribution, assessed by compartment.

Participants receiving semaglutide demonstrated a reduction in abdominal VAT (β -30.82 cm²; 95% CI, -50.13 to -11.51; P < .05) compared with placebo. Additional reductions were observed in abdominal subcutaneous adipose tissue (β -42.01 cm²; 95% CI, -75.49 to -8.52; P < .05) and total body fat (-0.21 kg log-transformed; 95% CI, -0.33 to -0.08; P < .05), indicating a broader fat-lowering effect. Safety profiles were generally comparable between groups (absolute risk difference 0.1111; 95% CI, -0.0727 to 0.2869); however, one case of grade 4 lipase elevation and two cases of cholelithiasis (grades 1 and 2) were noted in the semaglutide group, suggesting the need for additional studies investigating semaglutide’s potential adverse events in this patient population.

The study’s limitations include its single-site setting, small sample size, and relatively short follow-up period.

“Semaglutide holds promise as an effective treatment for HIV-associated lipohypertrophy,” the authors concluded, “but the potential risk of serious adverse events deserves further scrutiny in large trials in people with HIV.”

Reference

Eckard AR, Wu Q, Sattar A, et al. Once-weekly semaglutide in people with HIV-associated lipohypertrophy. Lancet Diabetes Endocrinol. 2024;12(8):523-534. doi:10.1016/S2213-8587(24)00150-5.