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Semaglutide Improves Cognitive Function in HIV,
Effect Mediated by Decrease in Inflammation
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CROI 2025 March 9-12 SF
Addressing issues of increased visceral adiposity accumulation, including in the liver and muscle, in people living with HIV is imperative because they are associated with increased diabetes and cardiovascular disease, McComsey said. "Cognitive dysfunction is also very prevalent in HIV, and data had previously shown an association between cognitive dysfunction and increased visceral adiposity and inflammation in HIV; therefore, adding cognitive assessment to this trial was an important endpoint," she said.
In the current study, Atieh and colleagues examined the impact of semaglutide on neurocognitive function and any mediation from improved adiposity and inflammatory markers.
At 32 weeks, the semaglutide group showed significant increases in visuospatial, naming/language, and delayed recall scores compared to the placebo group (P = .01, P = .05, and P = .04, respectively). However, only the visuospatial score retained significance after adjusting for sex and CD4 count (P = .05).
The researchers then considered weight, visceral adipose tissue, hs-CRP, and other inflammatory markers as potential mediators of visuospatial improvement. The total natural direct effect of semaglutide had a significant effect on the visuospatial score while accounting for potential changes in hs-CRP levels (P = .04), but no mediating effect was noted for changes in total or central adiposity.
The researchers predicted that cognitive dysfunction would improve on GLP-1 RA and that this effect would be mediated by the attenuation of inflammation and in visceral adiposity, McComsey told Medscape Medical News. "The latter did not pan out in our analysis; decreases in weight and visceral adiposity on GLP-1 RA did not mediate the effect of GLP-1 RA on cognition," she said.
"Larger and longer studies are needed to better understand the full effect of GLP-1 RA on cognitive impairment," she said. "Although we used Cognivue to objectively assess cognitive function, it would be important to repeat the study with another method of assessing cognition to ensure reproducibility," she added.
"I do not think this is something ready for widespread clinical use," Cennimo said. However, the current study may shed some light onto the underlying causes of neurocognitive decline and open up further research to refine treatments, he said.
https://www.medscape.com/viewarticle/semaglutide-shows-promise-improving-cognition-adults-hiv-2025a10006j7
CROI webcast: https://www.croiwebcasts.org/console/player/54289?mediaType=slideVideo&
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