Resmetirom won FDA accelerated approval for MASH in March 2024, giving it more than a year on the market before semaglutide 2.4 mg followed via the same pathway in August 2025. Real-world data presented at AASLD’s Liver Meeting 2026 this week now put the two drugs side by side, and the weight and glycemic numbers favor semaglutide by a margin that clinicians will have trouble ignoring.
The larger of the two retrospective analyses, PLATINUM-Truveta, tracked 2,873 adults with MASH on semaglutide 2.4 mg and 2,285 on resmetirom across 30 US health systems. At six months, the semaglutide group lost an average of 18.9 lb versus 5.6 lb in the resmetirom group, a statistically significant gap. AST dropped 10.4 units per liter with semaglutide against 4.5 with resmetirom, and HbA1c fell 0.38 percentage points in the semaglutide arm while the resmetirom arm moved only 0.08 points. LDL was the one measure where resmetirom pulled ahead, falling 29.1 versus 13.7 units per liter, a between-group difference that reached statistical significance at six months.
The second study, RHODIUM-2, took a different comparison: 2,479 adults who initiated semaglutide against 70,702 adults with MASH who did not start any semaglutide therapy. At 12 months, semaglutide initiators lost 30.7 lb on average while the untreated group lost 2.4 lb. ALT fell 14.0 units per liter with semaglutide versus 3.8 without it, and among the subgroup that entered the study with elevated ALT, the enzyme reductions were even sharper: 24.3 versus 10.7 units per liter. The ESSENCE Phase 3 trial had already shown semaglutide meeting histological endpoints in MASH; these observational datasets extend the picture into routine clinical practice.
Both studies carry the standard limitations of retrospective, non-randomized designs: baseline characteristics differed between arms, follow-up was constrained by the recency of both approvals, and electronic medical record coding introduces noise. Unmeasured confounding remains a real possibility. Still, for the MASH specialist deciding between two accelerated-approval options in a patient carrying significant metabolic burden, the semaglutide-versus-resmetirom LDL comparison is the number most likely to shape individual treatment decisions, since it is the one place resmetirom held a consistent and significant advantage across both time points.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
