Trial review
SYNERGY-NASH: Tirzepatide for MASH With Liver Fibrosis, Explained
Tirzepatide for MASH with liver fibrosis
SYNERGY-NASH was a phase 2, dose-finding, multicentre, double-blind, randomised, placebo-controlled, 130 sites in 10 countries funded by Eli Lilly and Company. Tirzepatide was superior to placebo for MASH resolution without worsening of fibrosis. Reported resolution rates differ between secondary sources: one gives 51.8%, 62.8% and 73.3% at 5, 10 and 15 mg against 13.2% placebo; another gives 62% at 15 mg against 10% placebo. That figure belongs to the population, dose and 52 weeks shown below, and describes a group average rather than a prediction for any individual.
| Design | Phase 2, dose-finding, multicentre, double-blind, randomised, placebo-controlled, 130 sites in 10 countries |
|---|---|
| Population | Adults 18-80 with biopsy-confirmed MASH, stage F2 or F3 fibrosis, BMI 27-50, with or without type 2 diabetes, NAFLD activity score of 4 or above |
| Sample size | Randomised 1:1:1:1 |
| Intervention | Tirzepatide, once-weekly subcutaneous |
| Comparator | Placebo |
| Duration | 52 weeks |
| Primary endpoint | MASH resolution without worsening of fibrosis on liver histology at 52 weeks |
| Main result | Tirzepatide was superior to placebo for MASH resolution without worsening of fibrosis. Reported resolution rates differ between secondary sources: one gives 51.8%, 62.8% and 73.3% at 5, 10 and 15 mg against 13.2% placebo; another gives 62% at 15 mg against 10% placebo |
Show this figure as a table
| Step | Stage | What happens |
|---|---|---|
| 1 | Who was eligible | Adults 18-80 with biopsy-confirmed MASH, stage F2 or F3 fibrosis, BMI 27-50, with or without type 2 diabetes, NAFLD activity score of 4 or above |
| 2 | What they received | Tirzepatide, once-weekly subcutaneous |
| 3 | What it was compared against | Placebo |
| 4 | For how long | 52 weeks |
| 5 | What was measured first | MASH resolution without worsening of fibrosis on liver histology at 52 weeks |
| 6 | What the group average was | Tirzepatide was superior to placebo for MASH resolution without worsening of fibrosis. Reported resolution rates differ between secondary sources: one gives 51.8%, 62.8% and 73.3% at 5, 10 and 15 mg against 13.2% placebo; another gives 62% at 15 mg against 10% placebo |
| 7 | What it does not tell you | A group average is not a prediction for any individual reader. |
Show this figure as a table
| Item | Mean reduction | Evidence |
|---|---|---|
| Tirzepatide 15 mg (SURMOUNT-1) | 21% | Verified |
| Oral semaglutide 25 mg, adherent (OASIS 4) | 17% | Verified |
| Injectable semaglutide 2.4 mg (SURMOUNT-5) | 14% | Verified |
| Oral semaglutide 25 mg, treatment-policy (OASIS 4) | 14% | Verified |
| Orforglipron 17.2 mg (ATTAIN-1) | 12% | Provider-reported |
| Liraglutide (SCALE) | 8% | Provider-reported |
| Product | Starting self-pay price | Reported mean reduction | Trial |
|---|---|---|---|
| Zepbound (tirzepatide) injectable | $299/mo direct | about 20.9% at 15 mg | SURMOUNT-1, 72 weeks |
| Wegovy pill (oral semaglutide 25 mg) | $149/mo starting dose | 13.6–16.6% depending on estimand | OASIS 4, 64 weeks |
| Wegovy injectable (semaglutide 2.4 mg) | $349/mo maintenance | about 13.7% | SURMOUNT-5, 72 weeks |
| Foundayo (orforglipron) | $149/mo starting dose | about 11–12.4% at 17.2 mg | ATTAIN-1, 72 weeks |
- Obtain the NEJM full text and record the exact resolution rate per arm with its estimand. Two secondary sources conflict at the 15 mg arm (73.3% vs 62%).
Questions readers actually ask
Does this apply to compounded versions?
No. The trial studied an FDA-approved product at studied doses.
Is this drug as effective as tirzepatide?
By mean reduction across separate trials, no. The efficacy ladder above sets out the figures with the trial that produced each one.
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GLP-1 Tirzepatide Review. “SYNERGY-NASH: Tirzepatide for MASH With Liver Fibrosis, Explained.” S.J Partners LLC, 2026-07-24. https://glp1tirzepatidereview.com/research/synergy-nash/
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