Two drugs are FDA-approved for noncirrhotic MASH with F2–F3 fibrosis: resmetirom (Rezdiffra), a liver-targeted thyroid-hormone-receptor-β agonist and the first approval (March 2024); and semaglutide 2.4 mg (August 2025), a GLP-1 metabolic drug. Others — survodutide, FGF21 analogues, and lanifibranor — remain investigational. Both approved drugs treat, but do not cure, MASH.
Who the approved drugs are for
A MASH medication is not a fatty-liver drug for everyone. The approved agents target a specific group: adults with noncirrhotic MASH and F2–F3 fibrosis, meaning moderate-to-advanced scarring but not yet cirrhosis.
- Simple steatosis — fat without significant inflammation or fibrosis — usually does not need drug therapy, and metabolic and lifestyle care is the foundation.
- Cirrhosis (F4) is a different, later problem that the current approvals do not cover.
- Fibrosis stage, rather than the amount of fat, is what these drugs are trying to change, because fibrosis is what drives outcomes.
Whether a MASH drug applies to a particular person therefore cannot be known without fibrosis staging: FIB-4, then elastography, and sometimes biopsy. → FIB-4 · Elastography & Liver Fat · Liver Biopsy
Resmetirom (Rezdiffra) — the first approval
| Field | Detail |
|---|---|
| Class / mechanism | Liver-directed thyroid hormone receptor-β (THR-β) agonist; stimulates hepatic pathways that reduce liver fat and improve metabolism |
| Indication | First FDA-approved MASH drug (March 2024) — noncirrhotic MASH with F2–F3 fibrosis, with lifestyle change; European Commission–approved (Aug 2025) |
| Fibrosis stage | F2–F3 (not cirrhosis) |
| Efficacy | In MAESTRO-NASH (52-week histology), at the approved 80 mg/100 mg doses: MASH resolution 25.9%/29.9% vs 9.7% placebo and ≥1-stage fibrosis improvement 24.2%/25.9% vs 14.2% placebo (p<0.001); accelerated approval on surrogate endpoints |
| Safety | Mainly gastrointestinal (diarrhea, nausea) early on; label includes attention to lipids, potential eye and drug-interaction considerations |
| Monitoring | Per label — liver-related and other labs, and interaction awareness; ongoing fibrosis assessment |
| Limits | Accelerated approval; long-term outcome data maturing; not for cirrhosis or simple steatosis; taken alongside — not instead of — metabolic and lifestyle care |
Resmetirom is the first drug approved specifically for MASH, and its approval validated therapy targeted at fibrosis stage rather than at liver fat alone. Being liver-directed, it is not primarily a weight or glucose treatment, which is part of why it suits people whose metabolic disease is already controlled. → Fatty Liver & Weight Loss
Semaglutide 2.4 mg — the metabolic route
| Field | Detail |
|---|---|
| Class / mechanism | GLP-1 receptor agonist; weight loss plus improved insulin sensitivity and glucose control drive most of the liver benefit |
| Indication | FDA-approved for noncirrhotic MASH with F2–F3 fibrosis (accelerated approval, August 2025) — the first GLP-1 with a MASH indication |
| Fibrosis stage | F2–F3 (not cirrhosis) |
| Efficacy | In ESSENCE (72-week histology), MASH resolution 62.9% vs 34.3% placebo and ≥1-stage fibrosis improvement 36.8% vs 22.4% placebo (both p<0.001, both endpoints met); the fibrosis benefit is smaller in absolute terms but statistically significant |
| Safety | Mainly gastrointestinal (nausea, vomiting, diarrhea); boxed warning for medullary thyroid carcinoma/MEN2; pancreatitis caution; avoid in pregnancy; perioperative hold |
| Monitoring | Metabolic and weight response; standard GLP-1 cautions; ongoing fibrosis assessment |
| Limits | Accelerated approval; fibrosis effect more modest than inflammation effect; weight and liver fat tend to return if stopped |
Because semaglutide's liver effect is largely mediated by weight and metabolic improvement, one drug also addresses the obesity, diabetes and cardiovascular risk that usually accompany MASH, which is a genuine advantage where those drivers are present. → GLP-1 & Fatty Liver · MASLD & Cardiovascular Risk
Resmetirom and semaglutide compared
The two are not interchangeable, and they are sometimes complementary.
- Resmetirom is liver-directed, chosen primarily to treat the MASH and fibrosis themselves, including in people who do not need or cannot take a weight-loss drug.
- Semaglutide is metabolic, and is attractive when obesity, type 2 diabetes or high cardiovascular risk sit alongside the MASH, because one drug addresses several drivers.
- Both are accelerated approvals for the same F2–F3 window, both are added to lifestyle change, and neither is a cure.
Both also require ongoing fibrosis assessment on treatment. The choice between them is individualized to the whole metabolic picture, which is what an individual assessment at the practice establishes. → The San Diego Metabolic-Liver Program
The pipeline — investigational, not approved
These agents are in development and are not FDA-approved for MASH, so they are not available treatments:
- Survodutide — GLP-1/glucagon dual agonist; investigational for MASH. Grade D 🔴 (investigational)
- FGF21 analogues (for example efimosfermin, pegozafermin) — target hepatic metabolism and fibrosis pathways; investigational. Grade D 🔴
- Lanifibranor — pan-PPAR agonist; investigational for MASH. Grade D 🔴
- Others across the incretin, FGF21 and metabolic classes are in trials.
A field that had zero approved drugs before 2024 now has two and a deep pipeline, but a drug in trials is not an available drug, and effect sizes and safety for these agents are still being established. → The Next Generation of Obesity Drugs (/treat/future)
What these drugs do not do
- They do not replace sustained weight loss and metabolic care, which remain foundational. → Fatty Liver & Weight Loss
- They are not for simple steatosis or cirrhosis; the approvals target F2–F3 MASH.
- They do not remove the need for fibrosis staging and monitoring, which establishes whether a drug applies and tracks the response.
- They do not cure MASH. They improve inflammation and, more modestly, fibrosis, on accelerated approvals with outcome data still maturing.
What the evidence says: MASH drugs
- What we know: Two drugs are FDA-approved for noncirrhotic F2–F3 MASH — resmetirom (liver-directed THR-β) and semaglutide (metabolic GLP-1) — both improving MASH resolution and fibrosis versus placebo, with the fibrosis benefit smaller in absolute terms but statistically significant.
- What we think: Choice depends on the whole metabolic picture; combination and sequential strategies will likely be studied, and the pipeline will expand the options.
- What we don't know: Long-term hard-outcome data, comparative effectiveness, durability, and the eventual role of the pipeline agents.
Questions patients ask
What medications are approved for MASH?
Two: resmetirom (Rezdiffra), approved March 2024, and semaglutide 2.4 mg, approved August 2025 — both for noncirrhotic MASH with F2–F3 fibrosis. Grade A 🟢
What is resmetirom (Rezdiffra) and how does it work?
It is a liver-directed thyroid-hormone-receptor-β agonist that improves liver fat, MASH and fibrosis — the first drug approved specifically for MASH. Grade A 🟢
How is resmetirom different from semaglutide for MASH?
Resmetirom is liver-directed; semaglutide is a metabolic and weight drug whose liver benefit comes largely through weight loss. Different mechanisms, the same F2–F3 indication. Grade A 🟢 → GLP-1 & Fatty Liver
Who qualifies for a MASH drug?
Adults with noncirrhotic MASH and F2–F3 fibrosis, which requires fibrosis staging — FIB-4, elastography, sometimes biopsy — to establish. Grade A 🟢 → FIB-4
Are there side effects?
Resmetirom is mainly gastrointestinal, with lipid, eye and interaction considerations per label; semaglutide is mainly gastrointestinal with GLP-1 class cautions — thyroid boxed warning, pancreatitis, pregnancy. Grade A 🟢
What about survodutide, pegozafermin, or lanifibranor?
All investigational — in trials, not FDA-approved — so they are not available options. Grade D 🔴 → /treat/future
Written by Darius A. Schneider, MD, PhD · Board-Certified Endocrinologist (ECNU) · Last updated: Oct 2026 · References: FDA labeling for resmetirom (Rezdiffra, March 2024) and semaglutide 2.4 mg (MASH, Aug 2025); ESSENCE program; AASLD Practice Guidance on MASLD (2023). Regulatory and pipeline status re-verified on update — see verify-status note. Educational only; not individualized advice.
