Key points
- Who: adults with MASH and moderate-to-advanced fibrosis (F2–F3), no cirrhosis, alongside lifestyle change.
- Biopsy is not required. Non-invasive tests can identify likely F2–F3.
- Approvals differ by country. The Saudi 2026 consensus noted that resmetirom was not yet approved in Saudi Arabia; check current SFDA status before prescribing.
- Neither is approved for cirrhosis yet.
For the evidence, graded recommendations, a case and self-test questions, read Module 2: Choosing drug treatment for MASH.
1The two approved drugs
| Feature | Resmetirom | Semaglutide 2.4 mg |
|---|---|---|
| How it works | Liver-directed thyroid hormone receptor-β agonist | GLP-1 receptor agonist; weight loss and metabolic effects |
| Dose | 80 mg daily (<100 kg) or 100 mg daily (≥100 kg), by mouth | 2.4 mg weekly injection, built up over about 16 weeks |
| Trial | MAESTRO-NASH, 52 weeks | ESSENCE, 72 weeks |
| MASH resolution | 25.9% (80 mg) and 29.9% (100 mg) vs 9.7% placebo | 62.9% vs 34.3% placebo |
| Fibrosis improved ≥1 stage | 24.2% and 25.9% vs 14.2% | 36.8% vs 22.4% |
| Weight | Neutral | −10.5% vs −2.0% |
| Main side effects | Diarrhoea, nausea | Nausea, vomiting, diarrhoea, constipation |
| Watch for | Interactions: with a CYP2C8 inhibitor such as clopidogrel, lower the dose (80 mg if ≥100 kg, 60 mg if <100 kg). Statin caps: rosuvastatin and simvastatin 20 mg, atorvastatin and pravastatin 40 mg. Check TSH and free T4 if on levothyroxine. | Gallstones, pancreatitis history, muscle loss; not in pregnancy |
Approved in the US (resmetirom 2024, semaglutide 2025), the EU (resmetirom, conditional, 2025) and the UK (both, 2026). Long-term outcome trials are ongoing.
2Who qualifies for resmetirom (AASLD 2024)
| Recommended | Not recommended |
|---|---|
| MASLD with VCTE 8–15 kPa, or MRE 3.1–4.4 kPa, or biopsy-proven MASH F2–F3 | Cirrhosis, including VCTE >20 kPa or MRE >5 kPa |
| Values outside these ranges: individual decision by a liver specialist | Other active liver disease; alcohol >20 g/day (women) or >30 g/day (men); active thyroid disease |
The 2025 global consensus also allows treatment at 16–20 kPa if a second test excludes cirrhosis and there are no signs of portal hypertension.
3Choosing between them
- Obesity or type 2 diabetes needing treatment anyway: semaglutide treats both.
- Normal weight, GLP-1 not tolerated, or already on a GLP-1 drug: resmetirom is an option.
- Data on using both together are still limited.
4Monitoring resmetirom
- Safety: liver panel at 3, 6 and 12 months.
- Stop for liver injury: AST or ALT >5× the upper limit, or bilirubin >2.5 mg/dL with raised enzymes, among other label criteria.
- Response at 12 months, using the same test as at baseline (image-based stiffness preferred).
5Response at 12 months
| Finding | Action |
|---|---|
| LSM falls ≥25% on VCTE (≥20% on MRE), or ALT normalises or clearly improves | Benefit: continue |
| Small fall in LSM, no clear ALT change | Uncertain: re-optimise lifestyle, consider other options |
| Non-invasive tests worsen, or ALT keeps rising | No response: stop |
Based on the AASLD October 2024 update. The 2025 global consensus uses a ≥30% change in VCTE stiffness, and says ALT alone should not decide response.
6Other medicines
| Drug | Place in MASLD |
|---|---|
| Pioglitazone | Improved histology in trials. AASLD: can be considered with type 2 diabetes. EASL and the global consensus: safe, but use it for diabetes, not as a MASH treatment. Weight gain and fluid retention. |
| Vitamin E | AASLD: can be considered in selected people. Global consensus: only in selected people without diabetes or cirrhosis. EASL 2024: not recommended as MASH treatment. |
| Tirzepatide, other GLP-1 drugs | Use for diabetes or obesity. Liver data promising, not yet approved for MASH. |
| SGLT2 inhibitors | Use for diabetes, heart and kidney benefit. Not a liver treatment. |
| Metformin | Safe; no effect on histology. |
| Statins | Safe and recommended for heart risk, including compensated cirrhosis. |
| Ursodeoxycholic acid, silymarin, other supplements | Not recommended. |
Related topics
References
- Chen VL, et al. Resmetirom therapy for MASLD: October 2024 updates to AASLD Practice Guidance. Hepatology 2025;81(1):312–20. doi:10.1097/HEP.0000000000001112
- Younossi ZM, et al. Global consensus recommendations for MASLD and MASH. Gastroenterology 2025;169(5):1017–32. doi:10.1053/j.gastro.2025.02.044
- Harrison SA, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis (MAESTRO-NASH). N Engl J Med 2024;390:497–509. doi:10.1056/NEJMoa2309000
- Sanyal AJ, et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis (ESSENCE). N Engl J Med 2025;392:2089–99. doi:10.1056/NEJMoa2413258
- EASL–EASD–EASO Clinical Practice Guidelines on the management of MASLD. J Hepatol 2024;81:492–542. doi:10.1016/j.jhep.2024.04.031
- Rinella ME, et al. AASLD Practice Guidance on the clinical assessment and management of NAFLD. Hepatology 2023;77:1797–835. doi:10.1097/HEP.0000000000000323
- Noureddin M, et al. Expert panel recommendations: practical clinical applications for initiating and monitoring resmetirom in patients with MASH and moderate to noncirrhotic advanced fibrosis. Clin Gastroenterol Hepatol 2024;22(12):2367–77. doi:10.1016/j.cgh.2024.07.003
- Younossi ZM, et al. Updated global consensus recommendations for risk stratification, treatment initiation, and response monitoring in MASLD. Clin Gastroenterol Hepatol 2026;24(9):2333–47. doi:10.1016/j.cgh.2026.03.030
- British Liver Trust. Two MASH treatments receive MHRA approval, 2026. https://britishlivertrust.org.uk/new-hope-for-people-living-with-mash-as-two-treatments-receive-mhra-approval/
- Madrigal Pharmaceuticals. European Commission approval of Rezdiffra, 19 August 2025. https://ir.madrigalpharma.com/node/16716
How to cite this page
Desoky M. Drug treatment for MASH. Metabolic Liver Academy quick reference, version 1.0. Updated 2026-10-03. Available from: https://drmahmouddesoky.github.io/metabolic-liver-academy/ref/drugs.html
A summary of published guidelines for healthcare professionals. It does not replace clinical judgement, the full guidelines or local drug labels. Disclaimer.