Evidence map›Paper›PMID 41256006›Full record

ArticleResearch square2025

Epigenetic Aging and Treatment Response to Semaglutide in the SLIM LIVER Study.

Michael Corley, Alina Pang, Douglas Kitch, Amy Kantor, Fred Sattler, Pablo Belaunzaran-Zamudio, Todd Brown, Alan Landay, Jordan Lake, Kristine Erlandson

Registry-linked trialAbstract readPreprint
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04216589 (A Single-Arm, Open-Label, Pilot Study of Semaglutide for Non-Alcoholic Fatty Liver Disease), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04216589 phase2completednot on this map

A Single-Arm, Open-Label, Pilot Study of Semaglutide for Non-Alcoholic Fatty Liver Disease (NAFLD), a Metabolic Syndrome With Insulin Resistance, Increased Hepatic Lipids, and Increased Cardiovascular Disease Risk (The SLIM LIVER Study)

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2021 to 2023Enrolled51ConditionsHIV Infections, Non-Alcoholic Fatty Liver DiseaseArmsSemaglutide
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Michael CorleyUniversity of California, San Diego.
Alina PangUniversity of California, San Diego.
Douglas KitchHarvard T.H. Chan School of Public Health.
Amy KantorHarvard T.H. Chan School of Public Health.
Fred SattlerUniversity of Southern California Keck School of Medicine.
Pablo Belaunzaran-ZamudioNational Institute of Allergy and Infectious Diseases (contractor).
Todd BrownJohn Hopkins University School of Medicine.
Alan LandayUniversity of Texas Medical Branch.
Jordan LakeUTHealth Houston.
Kristine ErlandsonUniversity of Colorado- Anschutz Medical Center.

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
The AIDS Linked to the Intravenous Experience (ALIVE) StudyU01DA036297 · NIDA · JOHNS HOPKINS UNIVERSITY · PI Gregory D Kirk, Shruti H Mehta · 2014 to 2026
$28.9M
Mentoring in Endocrine and Metabolic Abnormalities in HIV and AgingK24AI120834 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T · 2015 to 2025
$1.8M
Mentoring Across Disciplines: Aging and Infectious Diseases with a Focus on MobilityK24AG082527 · NIA · UNIVERSITY OF COLORADO DENVER · PI Kristine Mace Erlandson · 2023 to 2026
$768k
NIAID NIH HHS K24 AI120834NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701NIA NIH HHS K24 AG082527NIDA NIH HHS U01 DA036297
6 · The paper itself

Abstract

Background: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), improves metabolic health and reduces liver fat in people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease (MASLD). Whether changes in epigenetic aging biomarkers reflect these clinical benefits remains unknown. Methods: We conducted a post hoc analysis of the SLIM LIVER study (ACTG A5371), a 24-week, single-arm trial of semaglutide (1.0 mg weekly) in PWH and MASLD. Epigenetic aging was assessed at baseline and 24 weeks using DNA methylation-based epigenetic clocks: DunedinPACE (pace of aging), PCGrimAge (mortality risk), and PCDNAmTL (methylation-derived telomere length). Participants were stratified by change in epigenetic markers (decrease vs. increase); clinical responses were compared across anthropometric, metabolic, and physical function outcomes. Results: We observed a stable pace of aging was maintained over 24 weeks (n=41) with a median change of DunedinPACE of +0.018 (IQR: -0.023 to +0.053), PCDNAmTL (median -0.006 kb; IQR: -0.073 to +0.054), and PCGrimAge (median +0.54 years; IQR: -0.33 to +1.26). Seventeen (41.5%) showed a decrease in DunedinPACE with significantly greater reductions in liver fat ( Conclusions: These findings provide preliminary evidence that semaglutide may modulate epigenetic age biomarkers, with DunedinPACE and PCDNAmTL tracking improvements in hepatic and physical function. Integration of epigenetic biomarkers into future trials may enhance gerotherapeutic precision by identifying individuals most likely to benefit from GLP-1RA therapy and by enabling minimally invasive monitoring of biological aging. Trial Registration: ClinicalTrials.gov ID: NCT04216589.

Indexed as

AgingDNA methylationEpigenetic clockEpigeneticsgeroscienceGLP-1HIVliverMASLDSemaglutide

Identifiers

PMID41256006
PMCPMC12622174

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.