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Study · Systematic review · 2025

9 results

Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.

Safwan M, Bourgleh MS, Alotaibi SA, Alotaibi E, Al-Ruqi A, El Raeya F

Annals of Saudi medicine1 Mar 2025Cited by 7 (Europe PMC)

PMID40189856 (opens in a new tab)PMCIDPMC12542916 (opens in a new tab)DOI10.5144/0256-4947.2025.129 (opens in a new tab)PepBankPUB-40189856
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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

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

Results from this study9

8 results from studies that gave the peptide. 8 results from people.

  1. 01HumanSystematic reviewSafety outcome

    In adults with obesity and without diabetes, tirzepatide increased the risk of gastrointestinal adverse events versus placebo.

    In plain wordsIn adults with obesity and without diabetes, tirzepatide caused more stomach and gut side effects than placebo.

    Peptide
    Tirzepatide
    Outcome
    IncreaseOverall gastrointestinal adverse events
    Study

    n: not reported in source

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

    Measurements

    risk ratio
    2.94 RR
    tirzepatide, GI adverse events

    Source sentences

    Summary
    with tirzepatide showing a greater risk (RR 2.94, 95% CI=2.61, 3.32)
    2 context sentences
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
    Summary · context
    Pooled analysis assessed the risks for GI, biliary, hepatic, and pancreatic adverse events.
  2. 02HumanSystematic reviewSafety outcome

    In adults with obesity and without diabetes, tirzepatide showed no significant biliary risk versus placebo.

    In plain wordsIn adults with obesity and without diabetes, tirzepatide showed no clear increase in gallbladder or bile duct problems compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    No significant changeBiliary adverse events
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Biliary adverse events · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    while tirzepatide showed no significant biliary risk.
    2 context sentences
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
    Summary · context
    Pooled analysis assessed the risks for GI, biliary, hepatic, and pancreatic adverse events.
  3. 03HumanSystematic reviewSafety outcome

    In adults with obesity and without diabetes, tirzepatide did not significantly increase hepatic adverse events versus placebo.

    In plain wordsIn adults with obesity and without diabetes, tirzepatide did not clearly increase liver side effects compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    No significant changeHepatic adverse events
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Neither agent significantly increased hepatic or pancreatic adverse events.
    2 context sentences
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
    Summary · context
    Pooled analysis assessed the risks for GI, biliary, hepatic, and pancreatic adverse events.
  4. 04HumanSystematic reviewSafety outcome

    In adults with obesity and without diabetes, tirzepatide did not significantly increase pancreatic adverse events versus placebo.

    In plain wordsIn adults with obesity and without diabetes, tirzepatide did not clearly increase pancreas side effects compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    No significant changePancreatic adverse events
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Neither agent significantly increased hepatic or pancreatic adverse events.
    2 context sentences
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
    Summary · context
    Pooled analysis assessed the risks for GI, biliary, hepatic, and pancreatic adverse events.
  5. 05HumanSystematic reviewSafety outcome

    In obese adults without diabetes, semaglutide raised overall GI adverse events versus placebo (RR 1.68).

    In plain wordsIn adults with obesity and no diabetes, semaglutide caused stomach and gut side effects more often than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseOverall GI adverse events, semaglutide
    Study

    n: not reported in source

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

    Measurements

    relative risk
    1.68 ratio
    semaglutide

    Source sentences

    Summary
    semaglutide (RR 1.68, 95% CI=1.46, 1.94).
    1 context sentence
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
  6. 06HumanSystematic reviewSafety outcome

    In obese adults without diabetes, semaglutide increased gallbladder-related disorders, particularly cholelithiasis, by over 2.6 times versus placebo.

    In plain wordsIn adults with obesity and no diabetes, semaglutide raised gallbladder problems, such as gallstones, more than 2.6 times compared with placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseGallbladder-related disorders, including cholelithiasis
    Study

    n: not reported in source

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

    Measurements

    relative risk
    > 2.6 fold
    semaglutide gallbladder-related disorders

    Source sentences

    Summary
    Semaglutide increased gallbladder-related disorders, particularly cholelithiasis, by over 2.6 times (95% CI=1.40, 4.82)
    1 context sentence
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
  7. 07HumanSystematic reviewSafety outcome

    In obese adults without diabetes, semaglutide did not significantly increase hepatic adverse events versus placebo.

    In plain wordsIn adults with obesity and no diabetes, semaglutide did not significantly raise liver side effects compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeHepatic adverse events
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Neither agent significantly increased hepatic or pancreatic adverse events.
    1 context sentence
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.
  8. 08HumanSystematic reviewSafety outcome

    In obese adults without diabetes, semaglutide did not significantly increase pancreatic adverse events versus placebo.

    In plain wordsIn adults with obesity and no diabetes, semaglutide did not significantly raise pancreas side effects compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changePancreatic adverse events
    Study

    n: not reported in source

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

    Source sentences

    Summary
    Neither agent significantly increased hepatic or pancreatic adverse events.
    1 context sentence
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.

Studies that did not test the peptide alone1

In this study, Semaglutide 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 Semaglutide.

  1. 09HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In obese adults without diabetes, semaglutide and tirzepatide pooled raised overall GI adverse events 1.86 times versus placebo.

    In plain wordsIn adults with obesity and no diabetes, the two drugs together, including semaglutide, caused stomach and gut side effects 1.86 times as often as placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseOverall GI adverse events, semaglutide and tirzepatide pooled
    Study

    n = 26,894

    Comparator
    Placebo
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal

    Measurements

    relative risk
    1.86 ratio
    semaglutide and tirzepatide pooled

    Source sentences

    Summary
    Overall GI adverse events were 1.86 times higher with *both* agents (95% CI=1.56, 2.21)
    1 context sentence
    Summary · context
    Thirteen RCTs involving 26 894 obese participants without diabetes were analyzed.

    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.

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 3 to 38Current

    28 Oct 2026, 02:04 UTC

    The same notice was added 36 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.

    Study results updated

  2. Version 2

    9 Oct 2026, 03:07 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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