Exploring the rates of Gastrointestinal adverse effects among five GLP-1 receptor agonists: A systematic review and Meta-Analysis of randomized controlled trials.

Joy B, Ramsamooj A, Ibrahim S, Wen J, Hsu N, Frezza E

Endocrine5 Jan 2026Cited by 2 (Europe PMC)

PMID41489846DOI10.1007/s12020-025-04494-3PepBankPUB-41489846

Publisher page PubMedAsk about this study

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: Publisher copyright. Results still quote short attributed sentences.

Results from this study16

4 results from studies that gave the peptide. 4 results from people.

01HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials of GLP-1 receptor agonists, tirzepatide carried the highest risk ratio for nausea in head-to-head comparisons.
In plain wordsIn a pooled analysis of trials, tirzepatide had the highest nausea risk of the five GLP-1 drugs compared.
Peptide
Tirzepatide
Outcome
IncreaseNausea risk ratio versus other GLP-1 RAs
Study
n: not reported in source
Comparator
Other GLP-1 receptor agonists (semaglutide, liraglutide, exenatide, dulaglutide)
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea
2 context sentences(design, population, supporting numbers)
Summary · context
A pair-wise meta-analysis evaluating the six most common GI AEs (nausea, vomiting, diarrhea, constipation, decreased appetite, and pancreatitis) among GLP-1 RAs was performed, along with a network meta-analysis comparing semaglutide, liraglutide, exenatide, dulaglutide, and tirzepatide to one anothe…
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
Report a problemFND-4148984601
02HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials of GLP-1 receptor agonists, tirzepatide carried the highest risk ratio for diarrhea in head-to-head comparisons.
In plain wordsIn a pooled analysis of trials, tirzepatide had the highest diarrhea risk of the five GLP-1 drugs compared.
Peptide
Tirzepatide
Outcome
IncreaseDiarrhea risk ratio versus other GLP-1 RAs
Study
n: not reported in source
Comparator
Other GLP-1 receptor agonists (semaglutide, liraglutide, exenatide, dulaglutide)
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea
2 context sentences(design, population, supporting numbers)
Summary · context
A pair-wise meta-analysis evaluating the six most common GI AEs (nausea, vomiting, diarrhea, constipation, decreased appetite, and pancreatitis) among GLP-1 RAs was performed, along with a network meta-analysis comparing semaglutide, liraglutide, exenatide, dulaglutide, and tirzepatide to one anothe…
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
Report a problemFND-4148984602
03HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials, semaglutide carried the highest risk ratio for vomiting among five GLP-1 receptor agonists.
In plain wordsIn head-to-head comparisons of five GLP-1 drugs, semaglutide had the highest risk of vomiting.
Peptide
Semaglutide
Outcome
IncreaseVomiting risk ratio in head-to-head comparison
Study
n: not reported in source
Comparator
Other GLP-1 receptor agonists (network meta-analysis)
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea while semaglutide carries the highest risk ratios for vomiting and constipation.
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
Report a problemFND-4148984615
04HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials, semaglutide carried the highest risk ratio for constipation among five GLP-1 receptor agonists.
In plain wordsIn head-to-head comparisons of five GLP-1 drugs, semaglutide had the highest risk of constipation.
Peptide
Semaglutide
Outcome
IncreaseConstipation risk ratio in head-to-head comparison
Study
n: not reported in source
Comparator
Other GLP-1 receptor agonists (network meta-analysis)
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea while semaglutide carries the highest risk ratios for vomiting and constipation.
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
Report a problemFND-4148984616

Studies that did not test the peptide alone12

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.

05HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including semaglutide) increased the risk of nausea versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including semaglutide, nausea was more common than with placebo.
Peptide
Semaglutide
Outcome
IncreaseNausea
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
2.9 RR
nausea vs placebo
Incidence
22.8%
nausea
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
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.
Report a problemFND-4148984603
06HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including liraglutide) increased the risk of nausea versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including liraglutide, nausea was more common than with placebo.
Peptide
Liraglutide
Outcome
IncreaseNausea
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
2.9 RR
nausea vs placebo
Incidence
22.8%
nausea
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
In this study, Liraglutide 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 Liraglutide.
Report a problemFND-4148984604
07HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including semaglutide) increased the risk of vomiting versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including semaglutide, vomiting was more common than with placebo.
Peptide
Semaglutide
Outcome
IncreaseVomiting
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
3.6 RR
vomiting vs placebo
Incidence
9.12%
vomiting
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
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.
Report a problemFND-4148984605
08HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including liraglutide) increased the risk of vomiting versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including liraglutide, vomiting was more common than with placebo.
Peptide
Liraglutide
Outcome
IncreaseVomiting
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
3.6 RR
vomiting vs placebo
Incidence
9.12%
vomiting
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
In this study, Liraglutide 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 Liraglutide.
Report a problemFND-4148984606
09HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including semaglutide) increased the risk of diarrhea versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including semaglutide, diarrhea was more common than with placebo.
Peptide
Semaglutide
Outcome
IncreaseDiarrhea
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
1.97 RR
diarrhea vs placebo
Incidence
13%
diarrhea
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
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.
Report a problemFND-4148984607
10HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including liraglutide) increased the risk of diarrhea versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including liraglutide, diarrhea was more common than with placebo.
Peptide
Liraglutide
Outcome
IncreaseDiarrhea
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
1.97 RR
diarrhea vs placebo
Incidence
13%
diarrhea
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
In this study, Liraglutide 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 Liraglutide.
Report a problemFND-4148984608
11HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including semaglutide) increased the risk of constipation versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including semaglutide, constipation was more common than with placebo.
Peptide
Semaglutide
Outcome
IncreaseConstipation
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
2.41 RR
constipation vs placebo
Incidence
7.39%
constipation
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
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.
Report a problemFND-4148984609
12HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including liraglutide) increased the risk of constipation versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including liraglutide, constipation was more common than with placebo.
Peptide
Liraglutide
Outcome
IncreaseConstipation
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
2.41 RR
constipation vs placebo
Incidence
7.39%
constipation
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
In this study, Liraglutide 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 Liraglutide.
Report a problemFND-4148984610
13HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including semaglutide) increased the risk of decreased appetite versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including semaglutide, reduced appetite was reported more often than with placebo.
Peptide
Semaglutide
Outcome
IncreaseDecreased appetite
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
3.51 RR
decreased appetite vs placebo
Incidence
2.61%
decreased appetite
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
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.
Report a problemFND-4148984611
14HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including liraglutide) increased the risk of decreased appetite versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including liraglutide, reduced appetite was reported more often than with placebo.
Peptide
Liraglutide
Outcome
IncreaseDecreased appetite
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
3.51 RR
decreased appetite vs placebo
Incidence
2.61%
decreased appetite
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
In this study, Liraglutide 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 Liraglutide.
Report a problemFND-4148984612
15HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including semaglutide) increased the risk of pancreatitis versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including semaglutide, pancreatitis was reported more often than with placebo.
Peptide
Semaglutide
Outcome
IncreasePancreatitis
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
2.24 RR
pancreatitis vs placebo
Incidence
1.07%
pancreatitis
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
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.
Report a problemFND-4148984613
16HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In randomized trials of adults with type 2 diabetes or obesity, pooled GLP-1 receptor agonists (including liraglutide) increased the risk of pancreatitis versus placebo.
In plain wordsAcross trials of GLP-1 drugs as a class, including liraglutide, pancreatitis was reported more often than with placebo.
Peptide
Liraglutide
Outcome
IncreasePancreatitis
Study
n = 57,684
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
2.24 RR
pancreatitis vs placebo
Incidence
1.07%
pancreatitis
Source sentences
Summary
All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and…
1 context sentence(design, population, supporting numbers)
Summary · context
101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies).
In this study, Liraglutide 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 Liraglutide.
Report a problemFND-4148984614

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.

Versions 4 to 39Current
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
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
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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Exploring the rates of Gastrointestinal adverse effects among five GLP-1 receptor agonists: A systematic review and Meta-Analysis of randomized controlled trials.

Summary

Results from this study16

Studies that did not test the peptide alone12

Version history

Subjects

Publication types

MeSH terms

Keywords