Semaglutide outpaces resmetirom on key MASH measures

Clinical takeaway: For patients with metabolic dysfunction associated steatohepatitis (MASH) who are candidates for either therapy, semaglutide was associated with greater short-term improvements in liver enzymes, weight, and HbA1c than resmetirom in a large real-world analysis. The findings may be particularly relevant for patients with significant obesity or metabolic comorbidities.

Semaglutide and resmetirom both received FDA approval for adults with MASH and F2-F3 fibrosis, but head-to-head comparative data are scarce. Real-world evidence may help clinicians understand how these therapies perform outside the controlled setting of clinical trials.

New data from the PLATINUM-Truveta study, to be presented at The Liver Meeting 2026 and not yet peer reviewed, compared outcomes among adults with MASH treated with semaglutide or resmetirom using electronic medical records from 30 U.S. health systems. Investigators identified 2,873 semaglutide-treated patients and 2,285 resmetirom-treated patients and followed changes in ALT, AST, body weight, and HbA1c over time.

Patients receiving semaglutide were younger on average (48 vs 59 years), more often women (67% vs 58%), and had higher baseline BMI (39 vs 34 kg/m²). To account for baseline differences, researchers used inverse probability weighting and multivariable adjustment.

In unadjusted analyses, semaglutide produced larger early reductions in liver enzymes, with ALT falling by 6 U/L after 1 month while ALT increased by 5 U/L with resmetirom. AST decreased by about 5 U/L with semaglutide but rose by 4 U/L with resmetirom. By 6 months, semaglutide users had lost about 20 lb compared with 4 lb for resmetirom users, and by 12 months weight loss reached roughly 32 lb versus 4 lb. HbA1c reductions were also greater with semaglutide at both 6 and 12 months. After statistical adjustment, semaglutide maintained significantly greater improvements in ALT, AST, weight, and HbA1c at 3 and 6 months.

“Patients treated with semaglutide achieved significantly greater reductions in ALT, AST, weight, and HbA1c compared to patients treated with resmetirom,” the investigators concluded.

Source: Arora P, et al. The Liver Meeting 2026 (AASLD) Abstract 2461. Real-world comparative effectiveness of semaglutide versus resmetirom on liver enzymes and cardiometabolic markers in patients with MASH; Novo Nordisk. (2026 Oct 26). Novo to present new liver data across Wegovy 2.4 mg and investigational efruxifermin at The Liver Meeting® (AASLD) 2026