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

Bhattarai HB, Paudel BS, Parajuli SR, Dahal K, Shah S, Bhattarai M, Baral B, Karki B, Basnet B, Bhandari A, Sah R, Khanal A, Ahmed K, McDonald P

Medicine1 Dec 2025Cited by 3 (Europe PMC)

PMID41465949PMCIDPMC12746972DOI10.1097/md.0000000000046671PepBankPUB-41465949

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Summary

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Text rights: CC BY-NC. Results still quote short attributed sentences.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanSystematic reviewSafety outcome
In studies of orforglipron, nausea was the most common side effect in all studied dose groups.
In plain wordsNausea was the most common side effect in all studied orforglipron dose groups.
Peptide
Orforglipron
Outcome
Not applicableNausea frequency
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
12 mg, 24 mg, 36 mg, and 45 mg · oralAs given in this study (human).
Source sentences
Summary
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.
2 context sentences(design, population, supporting numbers)
Summary · context
We performed a systematic review of the literature databases like PubMed, Cochrane, Embase, and clinicaltrials.gov until November 2023.
Summary · context
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.
Report a problemFND-4146594901
02HumanSystematic reviewSafety outcome
In the orforglipron studies, the reported side-effect odds ratio at 45 mg was 4.41, with a 95% CI of 2.90-6.71.
In plain wordsThe reported side-effect odds ratio for orforglipron 45 mg was 4.41. The abstract does not clearly identify its endpoint or comparator.
Peptide
Orforglipron
Outcome
Direction not reportedReported side-effect odds ratio
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
45 mg · oralAs given in this study (human).
Measurements
Odds ratio
4.41
orforglipron 45 mg
95% CI of side-effect odds ratio
2.9 to 6.71
orforglipron 45 mg
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
We performed a systematic review of the literature databases like PubMed, Cochrane, Embase, and clinicaltrials.gov until November 2023.
Summary · context
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.
Report a problemFND-4146594902
03HumanSystematic reviewSafety outcome
In the orforglipron studies, the reported side-effect odds ratio at 36 mg was 3.99, with a 95% CI of 2.22-7.18.
In plain wordsThe reported side-effect odds ratio for orforglipron 36 mg was 3.99. The abstract does not clearly identify its endpoint or comparator.
Peptide
Orforglipron
Outcome
Direction not reportedReported side-effect odds ratio
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
36 mg · oralAs given in this study (human).
Measurements
Odds ratio
3.99
orforglipron 36 mg
95% CI of side-effect odds ratio
2.22 to 7.18
orforglipron 36 mg
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
We performed a systematic review of the literature databases like PubMed, Cochrane, Embase, and clinicaltrials.gov until November 2023.
Summary · context
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.
Report a problemFND-4146594903
04HumanSystematic reviewSafety outcome
In the orforglipron studies, the reported side-effect odds ratio at 24 mg was 5.66, with a 95% CI of 3.39-9.45.
In plain wordsThe reported side-effect odds ratio for orforglipron 24 mg was 5.66. The abstract does not clearly identify its endpoint or comparator.
Peptide
Orforglipron
Outcome
Direction not reportedReported side-effect odds ratio
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
24 mg · oralAs given in this study (human).
Measurements
Odds ratio
5.66
orforglipron 24 mg
95% CI of side-effect odds ratio
3.39 to 9.45
orforglipron 24 mg
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
We performed a systematic review of the literature databases like PubMed, Cochrane, Embase, and clinicaltrials.gov until November 2023.
Summary · context
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.
Report a problemFND-4146594904
05HumanSystematic reviewSafety outcome
In the orforglipron studies, the reported side-effect odds ratio at 12 mg was 5.06, with a 95% CI of 3.31-7.73.
In plain wordsThe reported side-effect odds ratio for orforglipron 12 mg was 5.06. The abstract does not clearly identify its endpoint or comparator.
Peptide
Orforglipron
Outcome
Direction not reportedReported side-effect odds ratio
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
12 mg · oralAs given in this study (human).
Measurements
Odds ratio
5.06
orforglipron 12 mg
95% CI of side-effect odds ratio
3.31 to 7.73
orforglipron 12 mg
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
We performed a systematic review of the literature databases like PubMed, Cochrane, Embase, and clinicaltrials.gov until November 2023.
Summary · context
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.
Report a problemFND-4146594905

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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