Evidence mapPaperPMID 41042549Full record

Trial reportThe Journal of endocrinology2025

RISING STARS: Effects of a GLP-1 receptor polymorphism on responses to liraglutide.

Mona Mashayekhi, Bilgunay Ilkin Safa, Hui Nian, Jessica K Devin, Jorge L Gamboa, Chang Yu, Rui Chen, Joshua A Beckman, John R Koethe, Heidi J Silver and 3 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Mona MashayekhiVanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, Tennessee, USA.ORCID https://orcid.org/0000-0003-0331-2395
Bilgunay Ilkin SafaVanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, Tennessee, USA.
Hui NianVanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee, USA.
Jessica K DevinUCHealth Endocrinology, Yampa Valley Medical Center, Steamboat Springs, Colorado, USA.
Jorge L GamboaThe University of Alabama at Birmingham, School of Medicine, Division of Nephrology, Birmingham, Alabama, USA.
Chang YuNYU Grossman School of Medicine, Department of Population Health, New York, New York, USA.
Rui ChenVanderbilt University, Department of Molecular Physiology and Biophysics, Nashville, Tennessee, USA.
Joshua A BeckmanUTSouthwestern Medical Center, Department of Internal Medicine, Division of Vascular Medicine, Dallas, Texas, USA.
John R KoetheDepartment of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Heidi J SilverDepartment of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Kevin NiswenderVanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, Tennessee, USA.
James M LutherVanderbilt University Medical Center, Department of Medicine, Division of Clinical Pharmacology, Nashville, Tennessee, USA.
Nancy J BrownYale School of Medicine, New Haven, Connecticut, USA.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · VANDERBILT UNIVERSITY MEDICAL CENTER · 1995 to 2025
$32.7M
Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR002243 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$10.7M
Translational Analysis CoreP30DK058404 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2002 to 2025
$4.9M
SHOPP30EY008126 · VANDERBILT UNIVERSITY MEDICAL CENTER · 1989 to 2025
$4.0M
RESEARCH TRAINING IN DIABETICS AND ENDOCRINOLOGYT32DK007061 · VANDERBILT UNIVERSITY MEDICAL CENTER · 1986 to 2025
$1.8M
Vanderbilt Diabetes Research CenterP30DK020593 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$1.8M
Institutional Career Development CoreKL2TR002245 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$1.1M
The Effect of SGLT2 Inhibition on Adipose Tissue Inflammation and Endothelial FunctionK23HL159351 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$185k
NCATS NIH HHS KL2 TR002245NCATS NIH HHS UL1 TR002243NCI NIH HHS P30 CA068485NCRR NIH HHS G20 RR030956NCRR NIH HHS UL1 RR024975NEI NIH HHS P30 EY008126NHLBI NIH HHS K23 HL159351NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS T32 DK007061
6 · The paper itself

Abstract

Abstract: The rs6923761 (Gly168Ser) missense variant in the glucagon-like peptide-1 receptor (GLP-1R) has been associated with favorable anthropometric and metabolic parameters in individuals with obesity but decreased responsiveness to incretin-based therapies. Here, we performed a pre-specified analysis of a randomized-controlled trial in individuals with obesity and pre-diabetes comparing treatment with the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 inhibitor sitagliptin or hypocaloric diet, and evaluated the effects of the rs6923761 variant on outcomes. We found significantly greater weight loss to liraglutide with each copy of the variant allele present, indicating a gene dose effect. In addition, individuals with the variant allele exhibited a significant reduction in the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 after liraglutide treatment. There was no effect of genotype on fasting glucose after liraglutide treatment, yet individuals with the variant allele exhibited decreased responsiveness to liraglutide and hypocaloric diet in measurements of fasting insulin, C-peptide, glucagon, and HOMA-IR. In conclusion, we found that the GLP-1R rs6923761 variant exerts a dual impact on liraglutide efficacy-enhancing weight loss while diminishing metabolic benefits. The observed associations could be consistent with the constitutive activation of the GLP-1R in the presence of this variant with reduced activation/signaling in response to pharmacologic agents, a pattern that has been observed with the rs10305492 variant in animal models. Future studies are needed to investigate the molecular mechanisms of associations with the rs6923761 variant.

Indexed as

Glucagon-Like Peptide-1 ReceptorHypoglycemic AgentsLiraglutideObesityAdultBlood GlucoseFemaleGlucagon-Like Peptide-1 Receptor AgonistsHumansMaleMiddle AgedPolymorphism, Single NucleotideSitagliptin PhosphateWeight LossBlood GlucoseGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsLiraglutideSitagliptin PhosphateGLP-1 receptorliraglutidePAI-1rs6923761weight loss

Identifiers

PMID41042549
PMCPMC12556785

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.