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Study · Systematic review · 2025

4 results

Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review.

Takrori E, Peshin S, Singal S

Medicina (Kaunas, Lithuania)5 Nov 2025Cited by 6 (Europe PMC)

PMID41303824 (opens in a new tab)PMCIDPMC12654588 (opens in a new tab)DOI10.3390/medicina61111987 (opens in a new tab)PepBankPUB-41303824
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Summary

Background: With rising obesity rates, pharmacological interventions are increasingly used in non-diabetic adults. While being effective in managing weight, these agents frequently cause gastrointestinal (GI) side effects, affecting adherence and long-term outcomes. Objective: To systematically evaluate the frequency, severity, and types of GI adverse effects (AEs) associated with anti-obesity medications in obese adults without diabetes. Methods: Following PRISMA 2020 guidelines, PubMed, Google Scholar, BMJ, and Web of Science were searched (last search July 2025). Eligible studies included randomized controlled trials, non-randomized trials, cohort studies, cross-sectional, and case-control studies. Only reports of GI AEs in non-diabetic adults were included. Risk of bias was assessed using Cochrane RoB 2 and Newcastle-Ottawa scales. Results: Out of 733 articles screened, 12 studies met predefined inclusion criteria, including one large cohort of 18,386 participants, along with randomized and observational trials of smaller size. The most frequently reported GI symptoms were nausea, vomiting, diarrhea, and constipation, predominantly with GLP-1 receptor agonists such as semaglutide and tirzepatide, especially during dose escalation. Orlistat commonly linked to steatorrhea and flatulence, while phentermine was associated with reduced GI motility. Newer agents, including retatrutide and orforglipron, also demonstrated notable GI side effect profiles. Natural products and investigational agents reported fewer adverse events but lacked long-term data and standardized reporting. Limitations: Evidence was limited by heterogeneity in study design and inconsistent reporting of GI outcomes. Conclusion: GI side effects are common across anti-obesity medications, particularly GLP-1 receptor agonists. Although generally mild to moderate, these symptoms can impact adherence and lead to treatment discontinuation. Tailored titration schedules, proactive patient counseling, and standardized adverse event reporting may improve tolerability. Further research is warranted to evaluate long-term GI outcomes and compare safety across emerging pharmacologic agents.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

2 results from studies that gave the peptide. 2 results from people.

  1. 01HumanSystematic reviewSafety outcome

    In non-diabetic adults with obesity, retatrutide showed a notable gastrointestinal side effect profile in a systematic review of anti-obesity medications.

    In plain wordsIn adults with obesity and without diabetes, retatrutide had notable stomach and gut side effects, according to a review of studies.

    Peptide
    Retatrutide
    Outcome
    Direction not reportedGastrointestinal side effect profile
    Study

    n: not reported in source

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Newer agents, including retatrutide and orforglipron, also demonstrated notable GI side effect profiles.
    1 context sentence
    Summary · context
    Only reports of GI AEs in non-diabetic adults were included.
  2. 02HumanSystematic reviewSafety outcome

    In non-diabetic adults, the systematic review reported gastrointestinal side effects with orforglipron.

    In plain wordsIn non-diabetic adults, the systematic review reported gastrointestinal side effects with orforglipron.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedGastrointestinal side effect profile
    Study

    n: not reported in source

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Newer agents, including retatrutide and orforglipron, also demonstrated notable GI side effect profiles.
    2 context sentences
    Summary · context
    Eligible studies included randomized controlled trials, non-randomized trials, cohort studies, cross-sectional, and case-control studies.
    Summary · context
    Only reports of GI AEs in non-diabetic adults were included.

Studies that did not test the peptide alone2

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

  1. 03HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In non-diabetic adults with obesity, nausea, vomiting, diarrhea and constipation were the most frequent GI symptoms, mostly with GLP-1 receptor agonists such as semaglutide, especially during dose escalation.

    In plain wordsIn adults with obesity without diabetes, GLP-1 drugs as a class were linked to nausea, vomiting, diarrhea and constipation, mainly during dose increases.

    Peptide
    Semaglutide
    Outcome
    Not applicableGastrointestinal adverse effects (nausea, vomiting, diarrhea, constipation)
    Study

    n: not reported in source

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal

    Source sentences

    Summary
    The most frequently reported GI symptoms were nausea, vomiting, diarrhea, and constipation, predominantly with GLP-1 receptor agonists such as semaglutide and tirzepatide, especially during dose escalation.
    1 context sentence
    Summary · context
    To systematically evaluate the frequency, severity, and types of GI adverse effects (AEs) associated with anti-obesity medications in obese adults without diabetes.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  2. 04HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome

    In non-diabetic adults with obesity, nausea, vomiting, diarrhea and constipation were the most frequent GI symptoms, mostly with GLP-1 receptor agonists such as tirzepatide, especially during dose escalation.

    In plain wordsIn adults with obesity without diabetes, GLP-1 drugs as a class were linked to nausea, vomiting, diarrhea and constipation, mainly during dose increases.

    Peptide
    Tirzepatide
    Outcome
    Not applicableGastrointestinal adverse effects (nausea, vomiting, diarrhea, constipation)
    Study

    n: not reported in source

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal

    Source sentences

    Summary
    The most frequently reported GI symptoms were nausea, vomiting, diarrhea, and constipation, predominantly with GLP-1 receptor agonists such as semaglutide and tirzepatide, especially during dose escalation.
    1 context sentence
    Summary · context
    To systematically evaluate the frequency, severity, and types of GI adverse effects (AEs) associated with anti-obesity medications in obese adults without diabetes.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

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.

  1. Versions 29 to 46Current

    28 Oct 2026, 02:04 UTC

    The same notice was added 18 times, first on 14 Oct 2026, 05:01 UTC. The status did not change between them.

    Study results updated

  2. Version 28

    14 Oct 2026, 01:46 UTC

    Study data updated · source update from Europe PMC

  3. Versions 4 to 27

    13 Oct 2026, 21:46 UTC

    The same notice was added 24 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.

    Study results updated

  4. Versions 2 to 3

    9 Oct 2026, 03:07 UTC

    The same notice was added 2 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  5. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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