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MASH drug evidence has three separate layers: a product’s regulatory indication, a trial’s liver-biopsy findings and its longer-term clinical outcomes. A change in liver fat, resolution of steatohepatitis and improvement in fibrosis answer different questions. This tracker keeps those questions attached to the medicine, study and source that actually address them.
The selected records cover resmetirom, semaglutide and tirzepatide research. Resmetirom illustrates a liver-directed pathway outside the GLP-1 class; semaglutide connects metabolic-drug research with a specific liver indication. Tirzepatide’s cited phase 2 study belongs in the research ledger rather than being treated as a regulatory decision.
Sources checked: 25 October 2026. The approval matrix is limited to the dated US FDA decisions below. The trial matrix describes selected publications, not every ongoing programme or a personal treatment choice. Australian registration and subsidy remain separate checks.
MASH, MASLD and NASH: what changed in the names?
The 2023 multisociety nomenclature consensus introduced metabolic dysfunction-associated steatotic liver disease, or MASLD, and metabolic dysfunction-associated steatohepatitis, or MASH. MASH identifies the steatohepatitis component within that framework. Fibrosis describes scarring severity and is a separate part of a study’s population and endpoints.
Older primary papers and trial names use NAFLD or NASH. Their original titles and eligibility definitions still matter. Renaming MAESTRO-NASH in a summary would make the study harder to trace; automatically treating all older and newer populations as identical would also lose information.
FDA decision tracker: match the product to the liver indication
| Product | Dated FDA decision | Indication context | Evidence obligation |
|---|---|---|---|
| Rezdiffra: resmetirom | 14 March 2024 FDA announcement. | Adults with noncirrhotic NASH and moderate-to-advanced liver scarring, alongside the conditions in the authorised product information. Resmetirom targets a thyroid-hormone-receptor pathway. | Accelerated approval uses a surrogate endpoint; confirmatory evidence is required to establish clinical benefit. |
| Wegovy injection: semaglutide | 15 August 2025 accelerated-approval letter; NDA 215256/S-024. | Noncirrhotic MASH in adults with moderate-to-advanced fibrosis, consistent with stages F2–F3. This record identifies the injectable product and liver indication. | The label states that continued approval may depend on verification of clinical benefit. |
The FDA’s accelerated-approval follow-up table lists confirmatory liver-outcome requirements for both products. A requirement or future completion date is not a completed study result.
For semaglutide, the FDA describes continued follow-up to assess outcomes such as liver-related events, transplantation and death. The agency’s MASH explanation separates the interim biopsy evidence from that longer-term question.
Published trial dataset: keep the endpoint and denominator together
The results below come from different studies. They are presented as a traceable evidence ledger, not a ranking of medicines. The paper’s analysis population, follow-up and endpoint definition accompany every quantitative entry.
| Primary study | Analysis and timing | Selected reported findings | Interpretation limit |
|---|---|---|---|
| MAESTRO-NASH: resmetirom, 2024 NCT03900429 |
Phase 3; 966 participants in the paper’s primary analysis population, with biopsy-defined NASH and F1B–F3 fibrosis; week 52. | NASH resolution without fibrosis worsening: 25.9% and 29.9% across the two intervention groups, versus 9.7% with placebo. At least one-stage fibrosis improvement without worsening of the activity score: 24.2% and 25.9%, versus 14.2%. | Retain this paper’s population and activity-score definition. Its denominator is not automatically the denominator in a regulatory summary. |
| ESSENCE: semaglutide, 2025 NCT04822181 |
Phase 3 planned interim analysis of the first 800 participants; week 72. The broader trial assigned 1,197 participants. | Steatohepatitis resolution without fibrosis worsening: 62.9% versus 34.3% with placebo. Fibrosis reduction without steatohepatitis worsening: 36.8% versus 22.4%. | These are biopsy endpoints in participants with F2–F3 fibrosis. The interim analysis does not itself establish the final longer-term clinical-outcome result. |
| SYNERGY-NASH: tirzepatide, 2024 NCT04166773 |
Published phase 2 randomised, placebo-controlled MASH study. | The primary record addresses MASH resolution and fibrosis-related findings. It also links a 2026 correction record. | This row identifies the study rather than reproducing corrected numerical estimates or implying a liver-specific approval. Consult the primary publication and correction together. |
The MAESTRO-NASH paper reports 966 people in its primary analysis, whereas the FDA approval announcement describes an 888-subject analysis. Keep each count with its source and analysis definition. Taking the denominator from one document and a result from the other can produce a misleading summary.
The primary SYNERGY-NASH record flags a later erratum. Numerical estimates are omitted from this row; readers should consult the paper and correction together when checking a result. The study identifier is retained so the evidence remains traceable.
Endpoint decoder: liver fat, inflammation, fibrosis and clinical events
| Outcome category | What the measurement addresses | Question to ask |
|---|---|---|
| Liver-fat measurement | A measure of steatosis in the study’s chosen assessment. | Was inflammation, scarring or a clinical event also measured? |
| Steatohepatitis resolution | Whether a participant meets the protocol’s resolution criteria, often with a condition about no fibrosis worsening. | Which biopsy definition and analysis population produced the proportion? |
| Fibrosis improvement | A prespecified change in scarring stage with a study-specific condition about disease activity. | How large a stage change was required, and what could not worsen? |
| Clinical outcomes | Events such as progression, decompensation, transplantation or death, as defined in the protocol. | Are completed event results available, or is confirmatory follow-up still required? |
A result such as “62.9% achieved resolution” describes the proportion meeting a specified endpoint. It is not a 62.9% loss of body weight or liver fat. Likewise, an improvement by one fibrosis stage is a protocol-defined outcome, not a general statement that every aspect of liver disease has reversed.
Our trial-reading guide explains why the population, comparator, endpoint and handling of missing observations belong beside a headline number. The same principles apply when the primary outcome concerns liver tissue rather than body weight.
Can these studies tell us which drug is best?
A cross-trial table can reveal differences in research design and evidence maturity. A direct treatment ranking requires a more appropriate comparison. Here the studies differ in populations, timing, analysis sets and endpoint details; their percentages should not be treated as if they came from one shared experiment.
Safety also belongs in the comparison. Read adverse events, discontinuation and the full authorised labelling alongside the endpoint findings. This page does not supply a complete benefit–risk assessment, eligibility decision or administration plan.
Does a liver indication apply to every semaglutide product?
The Wegovy decision above concerns a named injectable formulation and indication. A product-specific decision should stay attached to that record. To investigate oral formulations, use the separate oral GLP-1 approval and trial tracker, which identifies different application records and obesity studies.
US FDA decisions also do not establish Australian registration or PBS subsidy. Our Australian GLP-1 status guide keeps those local questions separate. The obesity-trial tracker follows the wider metabolic pipeline without turning every programme into an approved indication.
Scope and maintenance
This edition selects two dated US regulatory decisions and three primary study records. It is not an exhaustive MASH pipeline or an automatically updated registry. The original publication and decision dates are retained; the 25 October source check does not make older findings new.
Maintenance triggers are a material regulator decision, revised product information, a new primary paper or correction, and completed confirmatory-outcome results. Updates should keep identifiers, analysis denominators and endpoint definitions intact. The clinical-trials hub provides the supporting methods and source-reading pathways.
Educational evidence resource. No personal diagnosis, medicine selection, dosing or purchasing guidance.
How to cite this article
MASH and MASLD Drug Evidence: FDA Decisions and Trial Tracker. Elite Peps Australia. Published 25 October 2026; updated 25 October 2026. https://elitepepsaustralia.com/mash-masld-drug-trial-evidence-tracker/
Source checks: Consult the primary studies, trial records and regulator documents linked in this article for current evidence and status. Publication and update dates do not by themselves indicate an evidence review.