Evidence mapPaperPMID 41329075Full record

ArticleDiabetes2026

Prolonged Semaglutide Treatment Reveals Stage-Dependent Changes to Feeding Behavior and Metabolic Adaptations in Male Mice.

Harsh Shah, Julio E Ayala

Abstract read
In one paragraph

Article in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Harsh ShahDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
Julio E AyalaDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.ORCID 0000-0003-3224-2365

Funding

Translational Analysis CoreP30DK058404 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2002 to 2025
$4.9M
Vanderbilt Diabetes Research CenterP30DK020593 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$1.8M
Molecular mechanisms mediating metabolic benefits of glucagon-like peptide-1 receptor agonistsR01DK132852 · NIDDK · VANDERBILT UNIVERSITY · 2024 to 2025
$1.1M
Vanderbilt Center for Metabolic Phenotyping in Live Models of Obesity and DiabetesU2CDK135073 · VANDERBILT UNIVERSITY · 2025 to 2025
$754k
NIDDK NIH HHS 2P30DK020593NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK132852NIDDK NIH HHS R01DK132852NIDDK NIH HHS U2C DK135073NIDDK NIH HHS U2CDK135073NIH HHS S10 OD028455NIH Office of the Director OD028455
6 · The paper itself

Abstract

Glucagon-like peptide 1 receptor (GLP-1R) agonists have transformed obesity treatment, but weight loss responses to these drugs vary widely. Elucidating behavioral and metabolic phenotypes throughout GLP-1R agonist treatment could identify mechanisms underlying this response spectrum. We characterized food intake, meal patterns, energy expenditure (EE), and substrate oxidation during prolonged semaglutide treatment and posttreatment recovery in obese male mice at room temperature (RT) and thermoneutral temperature (TN). Semaglutide-induced weight loss and posttreatment weight regain were similar at RT and TN. Weight loss was divided into three stages at both temperatures: rapid initial weight loss, slower gradual weight loss, and weight maintenance. Initial weight loss was marked by reduced food intake, smaller and less frequent meals, and increased lipid oxidation. Food intake gradually returned to pretreatment levels through increased meal frequency, whereas meal size remained suppressed. Lipid oxidation gradually decreased, whereas carbohydrate oxidation increased. Weight-adjusted EE remained constant and elevated in semaglutide- versus vehicle-treated mice, and locomotor activity increased throughout semaglutide treatment. Mice rapidly regained weight after treatment cessation as a result of increased food intake, meal size and frequency, carbohydrate oxidation, EE, and activity. Thus, semaglutide-induced weight loss and regain after treatment cessation involve dynamic, stage-specific changes in feeding behavior, EE, and substrate oxidation. ARTICLE HIGHLIGHTS: Although many studies have demonstrated acute behavioral and metabolic effects of glucagon-like peptide 1 receptor (GLP-1R) agonists, few have assessed long-term effects of these drugs on these phenotypes. We assessed changes in various behavioral and metabolic phenotypes throughout a 21-day treatment regimen with semaglutide and posttreatment. Weight loss in response to prolonged semaglutide treatment can be divided into distinct phases, and each phase is characterized by different effects on food intake, meal patterns, energy expenditure, and substrate oxidation. Our findings suggest that differences in behavioral changes and/or metabolic adaptations may underlie the degree of weight loss responsiveness to GLP-1R agonists.

Indexed as

Adaptation, PhysiologicalEnergy MetabolismFeeding BehaviorGlucagon-Like PeptidesHypoglycemic AgentsAnimalsEatingGlucagon-Like Peptide-1 Receptor AgonistsMaleMiceMice, Inbred C57BLWeight LossGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesHypoglycemic Agents

Identifiers

PMID41329075
PMCPMC12823338

What Socratic holds

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Registered trials

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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.