Efficacy and Safety of Dual and Triple Glucagon-Like Peptide-1-Based Polyagonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Meta-Analysis.

Santos Solis R, Baeza-Zapata AA, Negrete-Najar JP

Cureus29 Jun 2026

PMID42529769PMCIDPMC13418920DOI10.7759/cureus.111728PepBankPUB-42529769

Summary

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are strongly linked to obesity, insulin resistance, type 2 diabetes, and progressive liver fibrosis. Dual and triple glucagon-like peptide-1 (GLP-1)-based polyagonists may provide complementary hepatic and metabolic benefits, but their overall efficacy and safety have not been fully established. This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH. PubMed, the Cochrane Central Register of Controlled Trials, ScienceDirect, and Google Scholar were searched from inception through May 19, 2026. Dichotomous outcomes were pooled as risk ratios (RRs), and continuous outcomes were analyzed as mean differences (MDs), using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Six randomized controlled trials involving 961 participants were included. The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%). Treatment also produced a greater relative reduction in liver fat content (MD -44.60 percentage points, 95% CI -51.17 to -38.04; I² = 0%) and increased the likelihood of achieving at least a 30% relative reduction in liver fat by magnetic resonance imaging-proton density fat fraction (RR 4.71, 95% CI 3.04-7.30; I² = 22%). Body weight was significantly reduced, although heterogeneity was considerable (MD -9.14 percentage points, 95% CI -17.38 to -0.91; I² = 98%). Nausea, diarrhea, and vomiting were more frequent with polyagonists, but no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation. In conclusion, dual and triple GLP-1-based polyagonists improve histological and imaging-based hepatic outcomes in MASLD and MASH and may simultaneously address underlying metabolic dysfunction. However, gastrointestinal intolerance, pharmacological heterogeneity, the small number of trials, and limited follow-up warrant cautious interpretation. Larger phase 3 trials are needed to clarify drug-specific efficacy, long-term safety, and effects on liver-related and cardiovascular outcomes.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study30

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone30

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.

01HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including tirzepatide) increased MASH resolution or histological improvement without fibrosis worsening versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group improved liver inflammation more than placebo.
Peptide
Tirzepatide
Outcome
IncreaseMASH resolution or histological improvement without worsening of fibrosis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
3.32
pooled polyagonists vs placebo
Source sentences
Summary
The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976901
02HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including retatrutide) increased MASH resolution or histological improvement without fibrosis worsening versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group improved liver inflammation more than placebo.
Peptide
Retatrutide
Outcome
IncreaseMASH resolution or histological improvement without worsening of fibrosis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
3.32
pooled polyagonists vs placebo
Source sentences
Summary
The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976902
03HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including survodutide) increased MASH resolution or histological improvement without fibrosis worsening versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group improved liver inflammation more than placebo.
Peptide
Survodutide
Outcome
IncreaseMASH resolution or histological improvement without worsening of fibrosis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
3.32
pooled polyagonists vs placebo
Source sentences
Summary
The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976903
04HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including tirzepatide) increased fibrosis improvement without MASH worsening versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group improved liver scarring more often than placebo.
Peptide
Tirzepatide
Outcome
IncreaseFibrosis improvement without worsening of MASH
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
1.49
pooled polyagonists vs placebo
Source sentences
Summary
The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976904
05HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including retatrutide) increased fibrosis improvement without MASH worsening versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group improved liver scarring more often than placebo.
Peptide
Retatrutide
Outcome
IncreaseFibrosis improvement without worsening of MASH
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
1.49
pooled polyagonists vs placebo
Source sentences
Summary
The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976905
06HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including survodutide) increased fibrosis improvement without MASH worsening versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group improved liver scarring more often than placebo.
Peptide
Survodutide
Outcome
IncreaseFibrosis improvement without worsening of MASH
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
1.49
pooled polyagonists vs placebo
Source sentences
Summary
The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976906
07HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including tirzepatide) produced a greater relative reduction in liver fat than placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group cut liver fat more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseRelative reduction in liver fat content
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference in relative liver fat
−44.6 percentage points
pooled polyagonists vs placebo
Source sentences
Summary
Treatment also produced a greater relative reduction in liver fat content (MD -44.60 percentage points, 95% CI -51.17 to -38.04; I² = 0%)
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976907
08HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including retatrutide) produced a greater relative reduction in liver fat than placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group cut liver fat more than placebo.
Peptide
Retatrutide
Outcome
DecreaseRelative reduction in liver fat content
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference in relative liver fat
−44.6 percentage points
pooled polyagonists vs placebo
Source sentences
Summary
Treatment also produced a greater relative reduction in liver fat content (MD -44.60 percentage points, 95% CI -51.17 to -38.04; I² = 0%)
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976908
09HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including survodutide) produced a greater relative reduction in liver fat than placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group cut liver fat more than placebo.
Peptide
Survodutide
Outcome
DecreaseRelative reduction in liver fat content
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference in relative liver fat
−44.6 percentage points
pooled polyagonists vs placebo
Source sentences
Summary
Treatment also produced a greater relative reduction in liver fat content (MD -44.60 percentage points, 95% CI -51.17 to -38.04; I² = 0%)
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976909
10HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including tirzepatide) increased the likelihood of a liver fat reduction of at least 30% versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group made a large liver fat drop more likely than placebo.
Peptide
Tirzepatide
Outcome
IncreaseAt least 30% relative liver fat reduction by MRI-PDFF
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
4.71
pooled polyagonists vs placebo
Source sentences
Summary
increased the likelihood of achieving at least a 30% relative reduction in liver fat by magnetic resonance imaging-proton density fat fraction (RR 4.71, 95% CI 3.04-7.30; I² = 22%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976910
11HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including retatrutide) increased the likelihood of a liver fat reduction of at least 30% versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group made a large liver fat drop more likely than placebo.
Peptide
Retatrutide
Outcome
IncreaseAt least 30% relative liver fat reduction by MRI-PDFF
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
4.71
pooled polyagonists vs placebo
Source sentences
Summary
increased the likelihood of achieving at least a 30% relative reduction in liver fat by magnetic resonance imaging-proton density fat fraction (RR 4.71, 95% CI 3.04-7.30; I² = 22%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976911
12HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including survodutide) increased the likelihood of a liver fat reduction of at least 30% versus placebo.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group made a large liver fat drop more likely than placebo.
Peptide
Survodutide
Outcome
IncreaseAt least 30% relative liver fat reduction by MRI-PDFF
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Risk ratio
4.71
pooled polyagonists vs placebo
Source sentences
Summary
increased the likelihood of achieving at least a 30% relative reduction in liver fat by magnetic resonance imaging-proton density fat fraction (RR 4.71, 95% CI 3.04-7.30; I² = 22%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976912
13HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including tirzepatide) reduced body weight versus placebo, with considerable heterogeneity.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group lowered body weight more than placebo, but results varied a lot between trials.
Peptide
Tirzepatide
Outcome
DecreaseBody weight reduction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference in body weight
−9.14 percentage points
pooled polyagonists vs placebo
Source sentences
Summary
Body weight was significantly reduced, although heterogeneity was considerable (MD -9.14 percentage points, 95% CI -17.38 to -0.91; I² = 98%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976913
14HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including retatrutide) reduced body weight versus placebo, with considerable heterogeneity.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group lowered body weight more than placebo, but results varied a lot between trials.
Peptide
Retatrutide
Outcome
DecreaseBody weight reduction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference in body weight
−9.14 percentage points
pooled polyagonists vs placebo
Source sentences
Summary
Body weight was significantly reduced, although heterogeneity was considerable (MD -9.14 percentage points, 95% CI -17.38 to -0.91; I² = 98%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976914
15HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled dual and triple GLP-1-based polyagonists (including survodutide) reduced body weight versus placebo, with considerable heterogeneity.
In plain wordsIn adults with fatty liver disease, GLP-1-based multi-agonist drugs as a group lowered body weight more than placebo, but results varied a lot between trials.
Peptide
Survodutide
Outcome
DecreaseBody weight reduction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference in body weight
−9.14 percentage points
pooled polyagonists vs placebo
Source sentences
Summary
Body weight was significantly reduced, although heterogeneity was considerable (MD -9.14 percentage points, 95% CI -17.38 to -0.91; I² = 98%).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976915
16HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, nausea was more frequent with pooled dual and triple GLP-1-based polyagonists (including tirzepatide) than with placebo.
In plain wordsIn adults with fatty liver disease, nausea happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseNausea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976916
17HumanNot a test of Retatrutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, nausea was more frequent with pooled dual and triple GLP-1-based polyagonists (including retatrutide) than with placebo.
In plain wordsIn adults with fatty liver disease, nausea happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Retatrutide
Outcome
IncreaseNausea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976917
18HumanNot a test of Survodutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, nausea was more frequent with pooled dual and triple GLP-1-based polyagonists (including survodutide) than with placebo.
In plain wordsIn adults with fatty liver disease, nausea happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Survodutide
Outcome
IncreaseNausea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976918
19HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, diarrhea was more frequent with pooled dual and triple GLP-1-based polyagonists (including tirzepatide) than with placebo.
In plain wordsIn adults with fatty liver disease, diarrhea happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseDiarrhea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976919
20HumanNot a test of Retatrutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, diarrhea was more frequent with pooled dual and triple GLP-1-based polyagonists (including retatrutide) than with placebo.
In plain wordsIn adults with fatty liver disease, diarrhea happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Retatrutide
Outcome
IncreaseDiarrhea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976920
21HumanNot a test of Survodutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, diarrhea was more frequent with pooled dual and triple GLP-1-based polyagonists (including survodutide) than with placebo.
In plain wordsIn adults with fatty liver disease, diarrhea happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Survodutide
Outcome
IncreaseDiarrhea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976921
22HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, vomiting was more frequent with pooled dual and triple GLP-1-based polyagonists (including tirzepatide) than with placebo.
In plain wordsIn adults with fatty liver disease, vomiting happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseVomiting
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976922
23HumanNot a test of Retatrutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, vomiting was more frequent with pooled dual and triple GLP-1-based polyagonists (including retatrutide) than with placebo.
In plain wordsIn adults with fatty liver disease, vomiting happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Retatrutide
Outcome
IncreaseVomiting
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976923
24HumanNot a test of Survodutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, vomiting was more frequent with pooled dual and triple GLP-1-based polyagonists (including survodutide) than with placebo.
In plain wordsIn adults with fatty liver disease, vomiting happened more often with GLP-1-based multi-agonist drugs as a group than with placebo.
Peptide
Survodutide
Outcome
IncreaseVomiting
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Nausea, diarrhea, and vomiting were more frequent with polyagonists
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976924
25HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, serious adverse events did not differ significantly between pooled dual and triple GLP-1-based polyagonists (including tirzepatide) and placebo.
In plain wordsIn adults with fatty liver disease, serious side effects did not differ clearly between GLP-1-based multi-agonist drugs as a group and placebo.
Peptide
Tirzepatide
Outcome
No significant changeSerious adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976925
26HumanNot a test of Retatrutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, serious adverse events did not differ significantly between pooled dual and triple GLP-1-based polyagonists (including retatrutide) and placebo.
In plain wordsIn adults with fatty liver disease, serious side effects did not differ clearly between GLP-1-based multi-agonist drugs as a group and placebo.
Peptide
Retatrutide
Outcome
No significant changeSerious adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976926
27HumanNot a test of Survodutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, serious adverse events did not differ significantly between pooled dual and triple GLP-1-based polyagonists (including survodutide) and placebo.
In plain wordsIn adults with fatty liver disease, serious side effects did not differ clearly between GLP-1-based multi-agonist drugs as a group and placebo.
Peptide
Survodutide
Outcome
No significant changeSerious adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976927
28HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, adverse events leading to discontinuation did not differ significantly between pooled dual and triple GLP-1-based polyagonists (including tirzepatide) and placebo.
In plain wordsIn adults with fatty liver disease, stopping treatment because of side effects did not differ clearly between GLP-1-based multi-agonist drugs as a group and placebo.
Peptide
Tirzepatide
Outcome
No significant changeAdverse events leading to treatment discontinuation
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
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.
Show in the study text Report a problemFND-4252976928
29HumanNot a test of Retatrutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, adverse events leading to discontinuation did not differ significantly between pooled dual and triple GLP-1-based polyagonists (including retatrutide) and placebo.
In plain wordsIn adults with fatty liver disease, stopping treatment because of side effects did not differ clearly between GLP-1-based multi-agonist drugs as a group and placebo.
Peptide
Retatrutide
Outcome
No significant changeAdverse events leading to treatment discontinuation
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4252976929
30HumanNot a test of Survodutide aloneSystematic reviewSafety outcome
In adults with MASLD or MASH, adverse events leading to discontinuation did not differ significantly between pooled dual and triple GLP-1-based polyagonists (including survodutide) and placebo.
In plain wordsIn adults with fatty liver disease, stopping treatment because of side effects did not differ clearly between GLP-1-based multi-agonist drugs as a group and placebo.
Peptide
Survodutide
Outcome
No significant changeAdverse events leading to treatment discontinuation
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH.
Summary · context
Six randomized controlled trials involving 961 participants were included.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4252976930

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 5Current
27 Oct 2026, 16:32 UTC
Study data updated · source update from Europe PMC
Version 4
10 Oct 2026, 10:21 UTC
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

Efficacy and Safety of Dual and Triple Glucagon-Like Peptide-1-Based Polyagonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Meta-Analysis.

Summary

Results from this study30

Studies that did not test the peptide alone30

Version history

Subjects

Publication types

Keywords