Relationship Between Metabolic and Histological Responses in People With Metabolic Dysfunction- Associated Steatohepatitis With and Without Type 2 Diabetes: Participant-Level Exploratory Analysis of the SYNERGY-NASH Trial With Tirzepatide.

Caussy C, Cusi K, Rosenstock J, Bugianesi E, Thomas MK, Tang Y, Mather KJ, Loomba R, Sanyal AJ, Hartman ML

Diabetes care1 Dec 2025Cited by 4 (Europe PMC)

PMID41066427PMCIDPMC12635880DOI10.2337/dc25-1306PepBankPUB-41066427

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 study8

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

Studies that did not test the peptide alone8

In this study, Tirzepatide 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 Tirzepatide.

01HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, body weight reduction was greater in responders for MASH resolution (-16.0%) than in nonresponders (-7.0%).
In plain wordsIn adults with MASH, people whose liver disease resolved lost more weight (16.0%) than people whose disease did not resolve (7.0%).
Peptide
Tirzepatide
Outcome
Not applicableBody weight reduction in MASH resolution responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for MASH resolution
Analysis
Exploratory
Outcome group
Body weight · Liver
Measurements
Body weight change
−16%
MASH resolution responders
Body weight change
−7%
nonresponders
Source sentences
Summary
greater body weight reductions were observed in responders for MASH resolution (-16.0% vs. -7.0%; P < 0.001) and for fibrosis improvement (-13.6% vs. -9.8%; P = 0.023).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642701
02HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, body weight reduction was greater in responders for fibrosis improvement (-13.6%) than in nonresponders (-9.8%).
In plain wordsIn adults with MASH, people whose liver scarring improved lost more weight (13.6%) than people whose scarring did not improve (9.8%).
Peptide
Tirzepatide
Outcome
Not applicableBody weight reduction in fibrosis improvement responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for fibrosis improvement
Analysis
Exploratory
Outcome group
Body weight · Liver
Measurements
Body weight change
−13.6%
fibrosis improvement responders
Body weight change
−9.8%
nonresponders
Source sentences
Summary
and for fibrosis improvement (-13.6% vs. -9.8%; P = 0.023).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642702
03HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, HbA1c reduction was greater in MASH resolution responders (-1.2%) than in nonresponders (-0.6%).
In plain wordsIn adults with MASH, people whose liver disease resolved had a larger HbA1c fall (1.2%) than people whose disease did not resolve (0.6%).
Peptide
Tirzepatide
Outcome
Not applicableHbA1c reduction in MASH resolution responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for MASH resolution
Analysis
Exploratory
Outcome group
Glycemic control · Liver
Measurements
HbA1c change
−1.2%
MASH responders
HbA1c change
−0.6%
nonresponders
Source sentences
Summary
Reductions in HbA1c were greater for MASH responders (-1.2% vs. -0.6%; P < 0.001) and fibrosis responders (-1.2% vs. -0.7%; P = 0.004) than for nonresponders.
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642703
04HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, HbA1c reduction was greater in fibrosis improvement responders (-1.2%) than in nonresponders (-0.7%).
In plain wordsIn adults with MASH, people whose liver scarring improved had a larger HbA1c fall (1.2%) than people whose scarring did not improve (0.7%).
Peptide
Tirzepatide
Outcome
Not applicableHbA1c reduction in fibrosis improvement responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for fibrosis improvement
Analysis
Exploratory
Outcome group
Glycemic control · Liver
Measurements
HbA1c change
−1.2%
fibrosis responders
HbA1c change
−0.7%
nonresponders
Source sentences
Summary
and fibrosis responders (-1.2% vs. -0.7%; P = 0.004) than for nonresponders.
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642704
05HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, liver fat improved more in MASH resolution responders than in nonresponders.
In plain wordsIn adults with MASH, people whose liver disease resolved had a larger drop in liver fat than people whose disease did not resolve.
Peptide
Tirzepatide
Outcome
Not applicableLiver fat improvement in MASH responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for MASH resolution
Analysis
Exploratory
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
Compared with nonresponders, greater improvements in liver fat and measures of adipose tissue insulin sensitivity (adipose tissue insulin resistance index and adiponectin) were observed with MASH responders (P < 0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642705
06HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, the adipose tissue insulin resistance index improved more in MASH resolution responders than in nonresponders.
In plain wordsIn adults with MASH, fat tissue insulin sensitivity improved more in people whose liver disease resolved than in those whose disease did not.
Peptide
Tirzepatide
Outcome
Not applicableAdipose tissue insulin resistance index improvement in MASH responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for MASH resolution
Analysis
Exploratory
Outcome group
Glycemic control · Liver
Source sentences
Summary
Compared with nonresponders, greater improvements in liver fat and measures of adipose tissue insulin sensitivity (adipose tissue insulin resistance index and adiponectin) were observed with MASH responders (P < 0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642706
07HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis, adiponectin improved more in MASH resolution responders than in nonresponders.
In plain wordsIn adults with MASH, adiponectin improved more in people whose liver disease resolved than in those whose disease did not.
Peptide
Tirzepatide
Outcome
Not applicableAdiponectin improvement in MASH responders versus nonresponders
Study
n = 154
Comparator
Nonresponders for MASH resolution
Analysis
Exploratory
Outcome group
Glycemic control · Liver
Source sentences
Summary
Compared with nonresponders, greater improvements in liver fat and measures of adipose tissue insulin sensitivity (adipose tissue insulin resistance index and adiponectin) were observed with MASH responders (P < 0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642707
08HumanNot a test of Tirzepatide aloneRandomized controlled trialMechanism
In adults with MASH and fibrosis, normalization of liver fat was a significant mediator of both MASH resolution and fibrosis improvement in the tirzepatide trial.
In plain wordsIn adults with MASH, getting liver fat back to normal explained part of the MASH resolution and scarring improvement seen in the trial.
Peptide
Tirzepatide
Outcome
Not applicableNormalization of liver fat as mediator of MASH resolution and fibrosis improvement
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
In causal mediation analyses, normalization of liver fat was a significant mediator of both MASH resolution and fibrosis improvement.
2 context sentences(design, population, supporting numbers)
Summary · context
Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.
Summary · context
Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment.
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.
Report a problemFND-4106642708

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
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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MeSH terms

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