Semaglutide in people with HIV: reduces both central and peripheral fat worsening lipoatrophy

Results from a phase 2 placebo-controlled clinical study of the GLP-1 agonist semaglutide in people with HIV-associated lipohypertrophy support the potential for reducing central fat but caution that it might also worsen peripheral lipoatrophy.

The study randomised 104 participants on effective ART with BMI >25 kg/m² and lipohypertrophy, but without diabetes, to once-weekly subcutaneous semaglutide or placebo for 32 weeks. Semaglutide was titrated for the first eight weeks and then given at 10 mg.

The results included a 30% reduction in the primary outcome of changes in visceral abdominal adipose tissue (β −30.82 cm²[95% CI –50.13 to −11.51]).

Reductions were also reported in abdominal subcutaneous adipose tissue (β −42.01 cm², [95% CI: −75.49 to −8.52] % change −11.2%) and total body fat (natural logarithmic −0·21 kg [95% CI: −0·33 to −0·08] % change −18.9%).

Side effects were similar in each arm although one semaglutide-related grade 4 elevated lipase and two possibly related cases of cholelithiasis (grades 1 and 2) were observed.

Ekhard AR et al. Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial. Lancet Diabetes and Endocrinology. DOI: 10.1016/S2213-8587(24)00150-5. (01July 2024).