Trial review
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SYNERGY-NASH: The drug for MASH With Liver Fibrosis, Explained
This medicine 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. The active ingredient 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.
| 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 | The molecule, once-weekly subcutaneous |
| Comparator | Placebo |
| Duration | 52 weeks |
| Primary endpoint | MASH resolution without worsening of fibrosis on liver histology at 52 weeks |
| Main result | This GLP-1 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 |
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| 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. |
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| 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% | Reported |
| Liraglutide (SCALE) | 8% | 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 |
Frequently asked questions
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 Semaglutide Rx. “SYNERGY-NASH: Tirzepatide for MASH With Liver Fibrosis, Explained.” S.J Partners LLC, 2026-08-03. https://glp1semaglutiderx.com/research/synergy-nash/
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