Evidence mapPaperPMID 42250890Full record

ArticleGastroenterology2026

A Subphenotype of Obesity With Reduced Enteroendocrine Glucagon-Like Peptide 1 Synthesis and Enhanced Tirzepatide Response.

Alexander L Ticho, Alison N McRae, Lizeth Cifuentes, Thomas Fredrick, Diego Anazco, Maria A Espinosa, Juan M Garcia Cordova, Michael Romanos, Jose Villamarin, Stephen Johnson and 5 more

Abstract read
In one paragraph

Article in Gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Alexander L TichoPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Alison N McRaePrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Lizeth CifuentesPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Thomas FredrickPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Diego AnazcoPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Maria A EspinosaPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Juan M Garcia CordovaPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Michael RomanosPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Jose VillamarinPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Stephen JohnsonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
Ryan LennonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
Maria D Hurtado AndradeDivision of Endocrinology, Department of Medicine, Mayo Clinic, Jacksonville, Florida.
Jun ChenDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
Michael CamilleriPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Andres J AcostaPrecision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: acosta.andres@mayo.edu.

Funding

Phenotype-Tailored Lifestyle intervention for Obesity: A Randomized TrialR01DK139028 · MAYO CLINIC ROCHESTER · 2025 to 2025
$669k
A Randomized, placebo-controlled trial of the effects of Long-Acting GLP-1 or Dual Incretin (GLP-1 and GIP) Modulation on Gastrointestinal Functions and Relationship to Weight LossR01DK142606 · MAYO CLINIC ROCHESTER · 2025 to 2025
$323k
NIDDK NIH HHS K23 DK114460NIDDK NIH HHS R01 DK139028NIDDK NIH HHS R01 DK142606
6 · The paper itself

Abstract

BACKGROUND &

aimsObesity is a heterogeneous disease characterized by different pathophysiological and behavioral traits that influence response to glucagon-like peptide 1 (GLP-1)-based therapies. We previously identified an obesity phenotype characterized by fast gastric emptying (GE) and increased postprandial hunger. We aimed to elucidate pathophysiological mechanisms in this phenotype by evaluating plasma enteroendocrine hormones and mucosal gene expression and to evaluate treatment response to tirzepatide across subphenotypes.

methodsA total of 483 adults with obesity underwent solid meal GE (SGE) by scintigraphy, postprandial appetite assessment using a visual analogue scale, and plasma enteroendocrine hormone profiling. Gaussian mixed modeling identified phenotypic clusters. Associations with plasma short-chain fatty acids and fecal metagenomics were explored. A separate cohort (n = 31) underwent colonic mucosal biopsies with quantification of GCG (GLP-1) and PYY messenger RNA. Retrospective evaluation of weight loss in participants treated with tirzepatide among each cluster was performed (n = 61).

resultsThree clusters were identified based on SGE and GLP-1. One cluster demonstrated fast SGE, increased postprandial hunger, and discordantly low postprandial GLP-1 (termed dc-GE/GLP-1; n = 130 [26.9%]), as well as lower plasma peptide YY and cholecystokinin. dc-GE/GLP-1 showed higher plasma short-chain fatty acid levels, without significant differences in fecal microbial composition. Compared with concordant clusters (c-GE/GLP-1; n = 353 [73.1%]), dc-GE/GLP-1 had decreased mucosal messenger RNA expression of GCG (GLP-1) and PYY. At 6 months of tirzepatide, dc-GE/GLP-1 was associated with greater weight loss compared with c-GE/GLP-1 (21.5% vs 11.7%).

conclusionsWe identified a subphenotype of obesity with fast GE and discordantly low GLP-1 plasma levels, reduced mucosal hormone synthesis, and enhanced weight loss to tirzepatide. Further studies are needed to identify mechanisms contributing to GLP-1 deficiency in this subphenotype of obesity.

Indexed as

Appetite RegulationEnteroendocrine CellsGastric EmptyingPrecision Medicine

Identifiers

PMID42250890
PMCPMC13325417

What Socratic holds

Textmetadata
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.