SYNERGY-NASH

CompletedPhase 2Results posted

A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH)

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

112

Recruiting sites

—

Enrollment

190

actual

Study population

MASH / NAFLD / liver fibrosis, Obesity / overweight

Key I/E criteria

•BMI ≥27•HbA1c ≤9.5%•eGFR ≤30

Primary endpoint

•MASH resolution, no fibrosis worsening

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04166773

Org study ID17361

Secondary ID2019-001550-26

Secondary IDI8F-MC-GPHREli Lilly and Company

Timeline

Milestones

Study first posted2019-11-18actual

Study start2019-11-19actual

Primary completion2023-12-11actual

Study completion2024-01-10actual

Last update posted2025-01-24actual

Results first posted2025-01-24actual

Assets

Investigational agents

Tirzepatide

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosisObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

Eligibility criteria

•Participants must have a body mass index (BMI) ≥27 kilograms per square meter (kg/m²) and ≤50 kg/m² with stable body weight for at least 3 months

•Participants with or without type 2 diabetes mellitus (T2DM)

–If with T2DM, hemoglobin A1c (HbA1c) ≤9.5%

•Participants must be willing to undergo baseline and endpoint liver biopsies

•Participants must have histologic diagnosis of NASH with stage 2 or 3 fibrosis by liver biopsy

•Participants must not have known or suspected alcohol abuse (>14 units/week for women and >21 units/week for men) or active substance abuse

•Participants must not have evidence of cirrhosis or other forms of liver disease

•Participants must not have heart attack, stroke, or hospitalization for congestive heart failure in the past 6 months

•Participants must not have active cancer within the last 5 years

•Participants must not have uncontrolled high blood pressure

•Participants must not have renal impairment with estimated glomerular filtration rate (eGFR) <30 milliters/minute/1.73m²; for participants on metformin, eGFR <45 mL/min/1.73m²

•Participants must not have a diagnosis of type 1 diabetes

•Participants must not have a history of pancreatitis (acute or chronic)

•Participants must not have calcitonin ≥35 nanograms per liter

•Participant must not have family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (family is defined as a first degree relative)

•Female participants must not be pregnant, breast-feeding, or intend to become pregnant or of childbearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

MASH / liver

Weight & body composition

2 endpoints

Secondary/registry result

Mean Change From Baseline in Body Weight

Time frame:Baseline to Week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Kilogram (kg)	95% CI
5 mg Tirzepatide	-11.46	—
10 mg Tirzepatide	-14.22	—
15 mg Tirzepatide	-17.88	—
Placebo	-1.04	—

LS Mean difference (Final Values)-10.4295% CI-14.32 – -6.52p<0.001Mixed Models Analysis

LS Mean difference (Final Values)-13.1995% CI-17.05 – -9.32p<0.001Mixed Models Analysis

LS Mean difference (Final Values)-16.8495% CI-20.71 – -12.98p<0.001Mixed Models Analysis

Secondary/protocol endpoint

Mean Change From Baseline in Body Weight

Time frame:Baseline to Week 52

Body weight, absolute change (kg)

change from baseline, improvement

MASH / liver

10 endpoints

Primary/registry result

Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology

Time frame:Week 52

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Posted result

Group	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	51.84	—
10 mg Tirzepatide	63.13	—
15 mg Tirzepatide	73.92	—
Placebo	12.62	—

Odds Ratio (OR)7.4595% CI2.27 – 24.44p<0.001Regression, Logistic

Odds Ratio (OR)11.8695% CI3.59 – 39.11p<0.001Regression, Logistic

Odds Ratio (OR)19.6395% CI5.73 – 67.25p<0.001Regression, Logistic

Primary/protocol endpoint

Percentage of Participants With Absence of Nonalcoholic Steatohepatitis (NASH) With no Worsening of Fibrosis on Liver Histology

Time frame:Week 52

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Secondary/registry result

Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver Histology

Time frame:Week 52

Fibrosis ≥1-stage improvement, no MASH worsening

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	59.21	—
10 mg Tirzepatide	53.35	—
15 mg Tirzepatide	54.3	—
Placebo	32.51	—

Odds Ratio (OR)3.0195% CI1.15 – 7.90p0.025Regression, Logistic

Odds Ratio (OR)2.3795% CI0.92 – 6.13p0.074Regression, Logistic

Odds Ratio (OR)2.4795% CI0.95 – 6.40p0.063Regression, Logistic

Secondary/registry result

Percentage of Participants With ≥1 Point Increase in Fibrosis Stage on Liver Histology

Time frame:Week 52

threshold achievement, event

Posted result

Group	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	12.04	—
10 mg Tirzepatide	9.81	—
15 mg Tirzepatide	5.53	—
Placebo	13.03	—

Odds Ratio (OR)0.9195% CI0.25 – 3.40p0.893Regression, Logistic

Odds Ratio (OR)0.7395% CI0.18 – 2.87p0.647Regression, Logistic

Odds Ratio (OR)0.3995% CI0.08 – 1.91p0.246Regression, Logistic

Secondary/registry result

Percentage of Participants That Achieve a ≥2 Point Decrease in NAFLD (Non-alcoholic Fatty Liver Disease) Activity Score (NAS) on Liver Histology, With ≥1 Point Reduction in at Least 2 NAS Components

Time frame:Week 52

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	81.02	—
10 mg Tirzepatide	86.55	—
15 mg Tirzepatide	88.77	—
Placebo	38.09	—

Odds Ratio (OR)6.9495% CI2.41 – 20.00p<0.001Regression, Logistic

Odds Ratio (OR)10.4695% CI3.36 – 32.61p<0.001Regression, Logistic

Odds Ratio (OR)12.8595% CI3.87 – 42.65p<0.001Regression, Logistic

Secondary/registry result

Mean Absolute Change From Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

Time frame:Baseline to Week 52

Liver fat content, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), absolute percentage of liver fat	95% CI
5 mg Tirzepatide	-10.12	—
10 mg Tirzepatide	-10.15	—
15 mg Tirzepatide	-11.34	—
Placebo	-1.31	—

LS Mean difference (Final Values)-8.8195% CI-12.04 – -5.58p<0.001Mixed Models Analysis

LS Mean difference (Final Values)-8.8395% CI-11.93 – -5.73p<0.001Mixed Models Analysis

LS Mean difference (Final Values)-10.0295% CI-13.17 – -6.87p<0.001Mixed Models Analysis

Secondary/protocol endpoint

Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of NASH on Liver Histology

Time frame:Week 52

Fibrosis ≥1-stage improvement, no MASH worsening

categorical status, improvement

Secondary/protocol endpoint

Percentage of Participants With ≥1 Point Increase in Fibrosis Stage on Liver Histology

Time frame:Week 52

threshold achievement, event

Secondary/protocol endpoint

Time frame:Week 52

threshold achievement, improvement

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Liver Fat Content by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

Time frame:Baseline to Week 52

Liver fat content, change

change from baseline, improvement

Publications (4)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Efficacy of tirzepatide, lanifibranor, and resmetirom in metabolic dysfunction-associated steatotic liver disease: a meta-analysis of high-quality randomized controlled trials.
Internal and emergency medicine2026 Mar 31PMID41917519doi:10.1007/s11739-026-04326-wvia pubmed nct search
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.
Diabetes care2025 Dec 1PMID41066427doi:10.2337/dc25-1306via pubmed nct search
Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.
The New England journal of medicine2024 Jul 25PMID38856224doi:10.1056/NEJMoa2401943via clinicaltrials gov reference derived + pubmed nct search
Research Progress on the GIP/GLP-1 Receptor Coagonist Tirzepatide, a Rising Star in Type 2 Diabetes.
Journal of diabetes research2023 (year)PMID37096236doi:10.1155/2023/5891532via pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.