Effects of Semaglutide on Cognitive Function in People With HIV: A Randomized, Controlled Trial

Area of Science:

• Neuroscience
• Immunology
• Endocrinology

Background:

• People with HIV (PWH) face higher risks of visceral adiposity, inflammation, and cognitive decline.
• Previous research showed semaglutide reduced adiposity and inflammation markers in PWH with lipohypertrophy.

Purpose of the Study:

• To investigate semaglutide's effect on cognitive function in PWH.
• To determine if changes in adiposity or inflammation mediate semaglutide's impact on cognition.

Main Methods:

• A 32-week, randomized, double-blind, placebo-controlled phase 2b trial involving PWH on antiretroviral therapy.
• Participants received subcutaneous semaglutide or placebo, with cognitive function, body composition, and inflammatory markers assessed.
• Causal mediation analysis examined direct and indirect effects on cognitive scores via adiposity and inflammation.

Main Results:

• Semaglutide significantly improved visuospatial, naming/language, and delayed recall scores compared to placebo (p = 0.01, 0.05, 0.04).
• Visuospatial scores remained significant after adjusting for sex and CD4 count (p=0.05).
• Semaglutide demonstrated a direct positive effect on visuospatial scores, mediated by reduced inflammation markers like hs-CRP and sCD163 (p=0.04).

Conclusions:

• Semaglutide may positively influence visuospatial cognitive function in PWH.
• The beneficial effects appear to be mediated through reductions in inflammation.