Nature communicationsMay 19, 2026

Semaglutide may slow biological aging in people with HIV-related fat buildup

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In adults with HIV-associated lipohypertrophy, semaglutide was linked to slower epigenetic aging over 32 weeks.

Evidence

This post hoc exploratory analysis of a 32-week randomized, double-blind, placebo-controlled phase 2b trial compared semaglutide (n=45) with placebo (n=39) and found adjusted reductions across multiple second- and third-generation DNA methylation aging clocks, including PhenoAge, PCGrimAge, GrimAge V2, OMICmAge, RetroAge, and DunedinPACE.

Caveat

Epigenetic aging was not a prespecified endpoint, and the modest HIV-specific sample with only 32 weeks of follow-up limits generalizability and clinical inference.

Simplified

Glucagon-like peptide-1 (GLP-1) receptor agonists have attracted interest as gerotherapeutics, yet clinical-trial evidence for their effects on biological aging is lacking. We report a post hoc exploratory epigenetic age analysis of a 32-week, randomized, double-blind, placebo-controlled phase 2b trial (NCT04019197) of semaglutide in adults with human immunodeficiency virus (HIV)-associated lipohypertrophy (semaglutide n = 45; placebo n = 39). The parent trial's primary endpoint was change in visceral adipose tissue, with secondary cardiometabolic and body-composition endpoints; epigenetic aging was not pre-specified. To address this gap, we profiled peripheral-blood DNA methylation (DNAm) at baseline and week 32 to assess semaglutide versus placebo on first-, second-, and third-generation epigenetic aging measures. In adjusted analyses, semaglutide reduced epigenetic aging across multiple second- and third-generation clocks, including PhenoAge ( - 4.9 years/year, p = 0.004), PCGrimAge ( - 3.1, p = 0.007), GrimAge V2 ( - 2.3, p = 0.009), OMICmAge ( - 2.2, p = 0.009), RetroAge ( - 2.2, p = 0.030), and DunedinPACE ( - 0.09 units, 9% slower, p = 0.01). Systems-based clocks showed parallel reductions in inflammation, brain, and heart aging measures. The post hoc design, modest sample size, HIV-specific cohort, and 32-week follow-up limit generalizability. Prospective trials are needed to determine whether GLP-1 receptor agonists can be repurposed as gerotherapeutics.

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Semaglutide may slow biological aging in people with HIV-related fat buildup

Abstract

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