Evidence map›Paper›PMID 42808923›Full record

ReviewNutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition2026

Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents.

Vikash Singhani, Muhammad Ehsan, Sara Valencia, Ahmed Nadeem, Eisha Moazzam, Winfield Scott Butsch, Samita Garg

Abstract readReview
In one paragraph

Review in Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 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

7 authors.

Vikash SinghaniDepartment of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID https://orcid.org/0000-0001-6063-1558
Muhammad EhsanDepartment of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
Sara ValenciaDepartment of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Ahmed NadeemDepartment of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Eisha MoazzamDepartment of Internal Medicine, King Edward Medical University, Lahore, Pakistan.
Winfield Scott ButschDepartment of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Samita GargDepartment of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID https://orcid.org/0009-0002-2493-1881

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation.

methodsThis narrative expert review synthesizes evidence from randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance data to characterize the incidence, mechanisms, and clinical implications of GI adverse effects across approved agents and late-stage pipeline therapies.

resultsNausea, vomiting, diarrhea, and constipation are established class effects, occurring in approximately 30%-50% of patients, typically during initiation and dose escalation. These events are generally mild to moderate and manageable with dose titration and dietary modification. Mechanisms include delayed gastric emptying, central activation of emetic pathways, altered intestinal motility, and physiologic effects of rapid weight loss itself. Randomized trial data are reassuring for acute pancreatitis, with no class-level excess risk demonstrated; pharmacovigilance signals are most plausibly explained by diagnostic misclassification rather than true causal risk. Cholelithiasis shows a probable class-level association, substantially mediated by weight loss rather than direct receptor signaling. Peri-procedural data show increased residual gastric volume without confirmed aspiration events. Preliminary data on late-stage pipeline agents (retatrutide, survodutide, and cagrilintide-semaglutide) suggest a similar GI adverse event profile to approved agents, though evidence remains largely limited.

conclusionGI adverse events with GLP-1-based therapies are predictable and manageable. A proactive, patient-centered approach is essential to optimize adherence, safety, and clinical outcomes as newer agents expand the therapeutic landscape.

Indexed as

Gastric Inhibitory PolypeptideGastrointestinal DiseasesGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsReceptors, Gastrointestinal HormoneDiabetes Mellitus, Type 2HumansObesityRandomized Controlled Trials as TopicTirzepatideGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsReceptors, Gastrointestinal HormoneTirzepatidediabetes mellitusdual GIP/GLP‐1 receptor agonistsgastrointestinal adverse eventsGLP‐1 receptor agonistsobesityorforglipronsemaglutidetirzepatide

Identifiers

PMID42808923
PMCPMC13622393

What Socratic holds

Textmetadata
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.