Evidence map›Paper›PMID 41465949›Full record

SynthesisMedicine2025

Gastrointestinal side effects of the non-peptide GLP-1 receptor agonists: A systematic review and meta-analysis.

Himal Bikram Bhattarai, Basanta Sharma Paudel, Sandesh Raman Parajuli, Krishna Dahal, Sangam Shah, Madhur Bhattarai, Bidisha Baral, Bibek Karki, Bibhusan Basnet, Amit Bhandari and 4 more

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

14 authors.

Himal Bikram BhattaraiDepartment of Medicine, Dubai London Hospital, Dubai, United Arab Emirates.
Basanta Sharma PaudelDepartment of Medicine, Tribhuvan University, Institute of Medicine, Maharajgunj, Nepal.
Sandesh Raman ParajuliDepartment of Medicine, Reading Hospital, West Reading, PA.
Krishna DahalDepartment of Medicine, Tribhuvan University, Institute of Medicine, Maharajgunj, Nepal.
Sangam ShahDepartment of Medicine, Tribhuvan University, Institute of Medicine, Maharajgunj, Nepal.ORCID 0000-0002-8203-3329
Madhur BhattaraiDepartment of Medicine, Tribhuvan University, Institute of Medicine, Maharajgunj, Nepal.ORCID 0000-0001-6382-1082
Bidisha BaralDepartment of Medicine, Ascension Saint Agnes Hospital, Baltimore, MD.
Bibek KarkiDepartment of Medicine, Hurley Medical Center, Michigan State University, Flint, MI.
Bibhusan BasnetDepartment of Medicine, Frye Regional Medical Center, Hickory, NC.
Amit BhandariDepartment of Medicine, St. John's Hospital, Springfield, IL.
Ranjit SahDepartment of Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India.
Amit KhanalDepartment of Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
Khalid AhmedDepartment of Medicine, Hurley Medical Center, Michigan State University, Flint, MI.
Philip McDonaldDepartment of Medicine, Hurley Medical Center, Michigan State University, Flint, MI.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlucagon-like peptide-1 (GLP-1) receptor agonists, commonly prescribed for diabetes mellitus and weight loss, often cause gastrointestinal side effects in both their oral and injectable forms. Recently, oral non-peptide GLP-1 receptor agonists like danuglipron and orforglipron, which are smaller and more stable, have been investigated. This study analyzes the gastrointestinal side effects of these newer, smaller molecules.

methodsWe performed a systematic review of the literature databases like PubMed, Cochrane, Embase, and clinicaltrials.gov until November 2023. Data related to different doses of oral danuglipron and orforglipron and their gastrointestinal side effects including nausea, vomiting, constipation, diarrhea, eructation, and dyspepsia were obtained. Analysis was done using RevMan v5.4 (The Cochrane Collaboration, Copenhagen, Denmark).

resultsWe included a total of 4 studies of which 2 each were for danuglipron and orforglipron. The oral doses of orforglipron studied were 12 mg, 24 mg, 36 mg, and 45 mg, with nausea being the most common side effect in all groups. For the 45 mg dose of orforglipron, the odds ratio (OR) was 4.41 (95% CI: 2.90-6.71), while the 36 mg dose had an OR of 3.99 (95% CI: 2.22-7.18). The OR for the 24 mg dose was 5.66 (95% CI: 3.39-9.45), and the 12 mg dose showed an OR of 5.06 (95% CI: 3.31-7.73). Oral danuglipron at doses of 80 mg and 120 mg were also studied. The 120 mg dose of danuglipron had a pooled OR of 4.38 (95% CI: 2.30-8.34) while the 80 mg dose had an OR of 3.69 (95% CI: 1.77-7.67) indicating a significant decrease in gastrointestinal side effects.

conclusionGastrointestinal side effects of the non-peptide GLP-1 receptor agonists were widely reported but less frequent compared to placebo/ standard treatment. There was no significant dose-dependent increase in the side effects of these medications.

Indexed as

Gastrointestinal DiseasesGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsDose-Response Relationship, DrugHumansNauseaGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic Agentsdanugliprongastrointestinal side effectsGLP-1 receptor agonistsobesityorforgliprontype 2 diabetes mellitus

Identifiers

PMID41465949
PMCPMC12746972

What OpenQuestion holds

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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 OpenQuestion graph.