Alimentary pharmacology & therapeuticsOct 23, 2025

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

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In MAESTRO-NASH, resmetirom benefit at 52 weeks was not reduced by background GLP-1RA or SGLT2 inhibitor use, and greater weight loss was linked to stronger responses.

Evidence

This secondary analysis of the randomized double-blind placebo-controlled phase 3 MAESTRO-NASH trial examined histology, MRI-PDFF, and liver stiffness at 52 weeks and found similar resolution and fibrosis improvement with resmetirom among patients on stable GLP-1RA or SGLT2i therapy, while resmetirom 100 mg with at least 5% weight loss showed higher MASH resolution (56.6% vs 33.8%) and fibrosis improvement (40.6% vs 31.5%).

Caveat

Because this was a secondary subgroup analysis and only 13%-17% of patients were on baseline GLP-1RA or SGLT2i therapy, the background-treatment comparisons are less definitive than the parent trial's primary results.

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 () 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 []) 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.

Key numbers

56.6%

Resolution Rate Increase

Resmetirom patients with ≥ 5% weight loss vs. < 5% weight loss.

40.6%

Fibrosis Improvement Rate Increase

Resmetirom patients with ≥ 5% weight loss vs. < 5% weight loss.

33.8%

Resolution Rate

Resmetirom patients with < 5% weight loss.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Funding

Competing interests

100%of authors

8 of 8

authors report competing interests

PubMed

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

Abstract

Key numbers

Full Text

Funding

Competing interests

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

Abstract

Key numbers

Full Text

Funding

Competing interests

Related papers

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