npj agingApr 21, 2026

Early study of biological aging and response to semaglutide treatment in fatty liver disease

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

Updated Apr 22, 2026

Abstract

In a trial with 41 participants, semaglutide treatment resulted in a median change of +0.018 in the DunedinPACE epigenetic aging metric over 24 weeks.

Participants with decreased DunedinPACE (41.5%) showed greater liver fat reduction.
A trend towards improved gait speed was observed in participants with decreased DunedinPACE.
Increased PCDNAmTL was associated with better gait speed.
These findings suggest potential early indicators of how semaglutide may influence biological aging.
Epigenetic biomarkers could play a role in personalizing GLP-1 receptor agonist therapy and monitoring aging.

Simplified

Semaglutide, a GLP-1 receptor agonist, improves metabolic health and reduces liver fat in people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease (MASLD). This post hoc analysis of the 24-week SLIM LIVER single-arm trial (ACTG A5371, No. NCT04216589, registered 02nd Jan 2020) in 41 PWH with MASLD receiving semaglutide (1.0 mg weekly) aimed to evaluate its effect on epigenetic aging and determine whether changes in epigenetic clocks associate with clinical responsiveness. Over 24 weeks, we observed DunedinPACE median change +0.018 (IQR -0.023 to +0.053), PCDNAmTL -0.006 kb (IQR -0.073 to +0.054), and PCGrimAge +0.54 years (IQR -0.33 to +1.26). Participants with decreased DunedinPACE (41.5%) showed greater liver fat reduction (p = 0.024) and trend towards improved gait speed (p = 0.081). Increased PCDNAmTL was associated with better gait speed (p = 0.012). These data suggest early signals of semaglutide responsiveness and relationships to epigenetic age biomarkers. Epigenetic biomarkers may enhance precision in GLP-1RA therapy and enable noninvasive monitoring of biological aging. Trial Registration: ClinicalTrials.gov ID: NCT04216589, registered 02nd Jan 2020.

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Funding

Competing interests

Competing interests: M.J.C. serves as a scientific advisor for TruDiagnostic. A.P.S.P. declares no disclosures. K.M.E. has received research funding from the NIH/NIA in support of the present manuscript; outside of the current work, she has received research funding from Gilead Sciences and has consulted for Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to her institution. T.T.B. has served as a consultant to Merck, ViiV Healthcare, EMD Serono, and Janssen. P.F.B.-Z. is the Division of AIDS medical officer for the study; however, his views are personal and do not represent the NIH/NIAID’s views.

PubMed

Early study of biological aging and response to semaglutide treatment in fatty liver disease

Abstract

Full Text

Funding

Competing interests

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