Direct study · 2024

SYNERGY-NASH

Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.

Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y, Brouwers B, Robins DA, Nikooie A, Bunck MC, Haupt A, Sanyal AJ, SYNERGY-NASH Investigators. · The New England journal of medicine

Study record

Population: 190 adults with biopsy-confirmed MASH and stage F2/F3 fibrosis.
Read source · Abstract-level extractionPrimary abstract — Methods and Results
Formulation: Sponsor-supplied tirzepatide or placebo in single-dose prefilled syringes. This is the registered study preparation, not proof of equivalence to research products or verification of every administered batch.
Read source · Study protocolProtocol I8F-MC-GPHR(d), Section 6.1, printed page 34
Route: Subcutaneous injection.
Read source · Abstract-level extractionPrimary abstract — Methods and Results
Dose & frequency: 5, 10 or 15 mg once weekly.
Read source · Abstract-level extractionPrimary abstract — Methods and Results
Study design: Phase 2, randomized double-blind placebo-controlled dose-finding trial.
Read source · Abstract-level extractionPrimary abstract — Methods and Results
Duration: 52 weeks.
Read source · Abstract-level extractionPrimary abstract — Methods and Results
Reported findings: MASH resolution without worsening fibrosis: 44%, 56%, 62% versus 10% placebo. Only 157 had evaluable week-52 biopsies; missing values were imputed.
Read source · Abstract-level extractionPrimary abstract — Methods and Results
Adverse events: Participants with serious adverse events — 5 mg Tirzepatide: 5/47; 10 mg Tirzepatide: 4/47; 15 mg Tirzepatide: 0/48; Placebo: 3/48. Events are not necessarily treatment-caused.
Read source · Registry resultsResults — Adverse Events, Serious Adverse Events summary; Baseline Up to Week 56
Monitoring: Protocol-planned monitoring: Screening physical examination with additional symptom-directed exams; sitting BP/pulse and triplicate 12-lead ECGs. Investigator laboratory review and adverse-event recording; abnormal lab repeat plan extends to one month after last dose. These planned assessments are not a personal monitoring schedule or proof every assessment occurred. Registry safety reporting and its observation window are cited separately under adverse events.
Read source · Study protocolSection 8.2, printed pages 49–50

What it supports

Addresses SYNERGY-NASH outcomes in its specified population and comparison.

What it does not establish

Histologic surrogate outcomes; does not establish reduced cirrhosis, liver failure or mortality. Abstract/registry extraction; unverified full-text details remain flagged.

Funding

Eli Lilly funded the study (primary abstract).

Publication and registry context

The registry reports modeled MASH/NASH resolution without worsening fibrosis in 51.84%, 63.13% and 73.92% versus 12.62%, using evaluable data before treatment discontinuation (39, 41, 40 and 35 participants). The publication estimates above use a different analysis with missing values imputed. Registry serious events through week 56 were 5/47, 4/47 and 0/48 versus 3/48; zero in one small arm does not establish absence of risk.

Inspect NCT04166773 results

Literature search cutoff: 2026-09-08 · Not independently clinically reviewed

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