SAN FRANCISCO — In sufferers with metabolic-associated steatotic liver illness or metabolic-associated steatohepatitis, resmetirom and glucagon receptor agonists each decreased liver fats and alanine aminotransferase ranges, researchers discovered.
For a meta-analysis offered at ENDO 2025, Hazem Ayesh, MD, MPH, adjunct scientific assistant professor of drugs at Indiana College and endocrinologist at Deaconess Well being System in Evansville, Indiana, and colleagues reviewed seven trials involving resmetirom (Rezdiffra, Madrigal Prescription drugs) or glucagon receptor agonists in sufferers with metabolic-associated steatotic liver illness (MASLD) or metabolic-associated steatohepatitis (MASH).
Resmetirom and glucagon receptor agonists had been tied to decrease liver fats and decreased alanine aminotransferase ranges for individuals with metabolic-associated steatotic liver illness or metabolic-associated steatohepatitis.
“MASLD/MASH now impacts roughly 25% of adults and can possible change into the No. 1 motive for liver transplant within the U.S.,” Ayesh informed Healio. “We have already got a number of section 2/3 medicine (GLP-1/glucagon co-agonists and the thyroid-beta agonist resmetirom) however nearly no head-to-head knowledge. A community meta-analysis lets us stack the proof from separate trials, rank remedies and provides clinicians a comparative image as an alternative of single-drug snapshots.”
Hazem Ayesh
The glucagon receptor agonists analyzed within the trials included cotadutide (AstraZeneca), retatrutide (Eli Lilly) and survodutide (Boehringer Ingelheim/Zealand). None have been authorized but by the FDA and cotadutide is not in improvement.
In contrast with placebo, resmetirom and glucagon receptor agonists demonstrated related reductions in MRI proton density fats fraction (resmetirom vs. placebo imply distinction, –47.59%; 95% CI, –72.84% to –22.35%; P = .0002; glucagon receptor agonists vs. placebo imply distinction, –48.93%; 95% CI, –96.81% to –1.05%; P = .0015), the researchers discovered.
Alanine aminotransferase (ALT) ranges had been tremendously decreased with resmetirom and glucagon receptor agonists in contrast with placebo, with glucagon receptor agonists being linked to the best reductions (resmetirom vs. placebo imply distinction, –20.08 U/L; 95% CI, –31.47 to –8.7; P = .0005; glucagon receptor agonists vs. placebo imply distinction, –28.97 U/L; 95% CI, –42.4 to –15.55; P < .0001), in response to the researchers.
There was no distinction in severe hostile occasions between resmetirom and placebo (RR = 1.1; 95% CI, 0.77-1.59), however there was a development towards elevated danger for severe hostile occasions for glucagon receptor agonists in contrast with placebo (RR = 2.38; 95% CI, 0.98-5.82), Ayesh and colleagues discovered.
“Glucagon receptor agonists (cotadutide, retatrutide, survodutide) produced the biggest drops in ALT and liver fats (MRI-PDFF). Resmetirom produced the strongest [aspartate aminotransferase], LDL and HDL enhancements and had fewer gastrointestinal (GI) negative effects,” Ayesh informed Healio. “Each courses elevated gentle nausea/diarrhea however didn’t elevate severe hostile occasion charges. Heterogeneity remains to be excessive; we’d like direct trials earlier than calling a winner.”
He mentioned glucagon receptor agonists swimsuit “sufferers with marked steatosis, excessive ALT and concurrent weight problems or sort 2 diabetes — offered the affected person can settle for a better fee of nausea and diarrhea,” whereas resmetirom “is the higher alternative for these whose precedence is fibrosis or lipid management, or who’re significantly delicate to GI negative effects, at all times on high of rigorous life-style remedy. We urgently want long-term, head-to-head trials powered for histology and outcomes, not simply enzymes and MRI fats. Value-effectiveness and entry may even matter as soon as the medicine attain market.”
For extra data:
Hazem Ayesh, MD, MPH, may be reached at hazimayesh@gmail.com.
Sources/Disclosures
Collapse
Andonie C, et al. OR21 – Adipose tissue, urge for food, and weight problems: The evolving panorama of MASLD: From pathophysiology to therapeutic improvements. Offered at: ENDO annual assembly; July 12-15, 2025; San Francisco.
Disclosures:
The authors report no related monetary disclosures.
