Effects of Resmetirom on Metabolic‐Dysfunction Associated Steatohepatitis in Patients With Weight Loss and/or Diabetes Taking Glucagon‐Like Peptide‐1 Receptor Agonists and Other Diabetes Therapies: A Secondary Analysis of the MAESTRO ‐ NASH Trial

Oct 23, 2025Alimentary pharmacology & therapeutics

Resmetirom's effects on fatty liver disease in patients with weight loss and/or diabetes using diabetes medications including GLP-1 receptor agonists

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Resmetirom (100 mg) led to 56.6% MASH resolution in patients with ≥ 5% weight loss after 52 weeks.

Patients receiving resmetirom showed improvement in liver conditions, regardless of background treatment with SGLT2 inhibitors or GLP-1 receptor agonists.
Weight loss of ≥ 5% was associated with higher rates of MASH resolution and fibrosis improvement in resmetirom-treated patients.
MRI-PDFF reduction was greater in patients with ≥ 5% weight loss compared to those with less than 5% weight loss.
Liver stiffness decreased more significantly in patients with ≥ 5% weight loss following resmetirom treatment.

AI simplified

BACKGROUND: MAESTRO-NASH, a randomised, double-blind, placebo-controlled, 54-month phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed metabolic-dysfunction associated steatohepatitis (MASH) and liver fibrosis achieved primary endpoints of MASH resolution with no worsening of fibrosis, and ≥ 1-stage improvement in fibrosis with no worsening of MASH at 52-weeks.

AIMS: The effects of resmetirom (80 or 100 mg) versus placebo were evaluated on Week 52 histological and biomarker endpoints in relation to background treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i), GLP-1 receptor agonists (GLP-1 RA), and/or ≥ 5% weight loss at Week 52.

METHODS: At baseline, 13%-17% of patients (all with type 2 diabetes mellitus [T2DM]) were on stable GLP-1 RA or SGLT2i therapy. Changes in liver histology, MRI-proton density fat fraction (MRI-PDFF), and liver stiffness were examined after 52 weeks of treatment.

RESULTS: No weight loss above baseline occurred with GLP-1 RA or SGLT2i therapy. SGLT2 and GLP-1 RA treated patients showed similar rates of MASH resolution and fibrosis improvement in combination with resmetirom as patients not on these therapies. Resmetirom-treated patients (100 mg) with weight loss (≥ 5%) compared with those with weight loss < 5% had higher rates of MASH resolution (56.6% vs. 33.8%), fibrosis improvement (40.6% vs. 31.5%), MRI-PDFF reduction (-69% vs. -46%), and liver stiffness reduction after 52 weeks of treatment (-4.6 kPa vs. -2.3 kPa).

CONCLUSIONS: The efficacy of resmetirom on multiple MASH endpoints was not impacted by background SGLT2i or GLP-1 RA treatment. Weight loss (≥ 5%) enhanced the efficacy of resmetirom.

TRIAL REGISTRATION: MAESTRO-NASH ClinicalTrials.gov number, NCT03900429.

Full Text

Full text is available at the source.

View full text ↗

Effects of Resmetirom on Metabolic‐Dysfunction Associated Steatohepatitis in Patients With Weight Loss and/or Diabetes Taking Glucagon‐Like Peptide‐1 Receptor Agonists and Other Diabetes Therapies: A Secondary Analysis of the MAESTRO ‐ NASH Trial

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief