Novo Nordisk: real‑world data link Wegovy 2.4 mg to lower liver enzymes, weight and HbA1c in adults with MASH
- At six months, semaglutide 2.4 mg users lost a mean 18.9 lb versus 5.6 lb with resmetirom (P<0.001) in PLATINUM‑Truveta.
- PLATINUM‑Truveta found greater AST reductions with semaglutide at six months (−10.4 vs −4.5 U/L; P<0.001) and larger HbA1c drops (−0.38 vs −0.08 percentage points; P<0.001).
- RHODIUM‑2 at 12 months reported semaglutide initiators lost 30.7 lb vs 2.4 lb in non‑initiators (adjusted between‑group difference −28.4 lb; P<0.001) and showed larger ALT and AST reductions (ALT difference −10.5 U/L; P<0.01).
- Both studies were retrospective, non‑randomised EMR analyses with potential unmeasured confounding, baseline differences, limited follow‑up and coding limitations; causality was not established.
Studies and cohorts
Two retrospective electronic‑medical‑record analyses presented at AASLD The Liver Meeting® 2026—PLATINUM‑Truveta and RHODIUM‑2—evaluated adults with metabolic dysfunction‑associated steatohepatitis (MASH) who initiated semaglutide 2.4 mg once weekly versus resmetirom (PLATINUM) or versus no semaglutide (RHODIUM). PLATINUM‑Truveta included 2,873 semaglutide and 2,285 resmetirom patients. RHODIUM‑2 included 2,479 semaglutide initiators and 70,702 non‑initiators. Data came from the Truveta database across ~30 US health systems covering June 2021–March 2026.
Key outcomes
PLATINUM‑Truveta reported adjusted mean weight loss at six months of −18.9 lb with semaglutide versus −5.6 lb with resmetirom (P<0.001), greater HbA1c reduction (−0.38 vs −0.08 percentage points; P<0.001), and larger AST declines (e.g., −10.4 vs −4.5 U/L at six months; P<0.001). ALT reductions were larger numerically for semaglutide but not statistically different at six months. RHODIUM‑2 found at 12 months an adjusted between‑group weight difference favoring semaglutide of −28.4 lb (P<0.001), and adjusted differences favoring semaglutide for ALT (−10.5 U/L; P<0.01) and AST (−7.3 U/L; P=0.001); paired HbA1c change at 12 months was −0.46 vs −0.09 percentage points.
Methods and limitations
Both analyses were observational and non‑randomized. Investigators applied generalized estimating equations and inverse‑probability‑of‑treatment weighting to reduce confounding, but groups differed at baseline and results are limited to patients with available follow‑up who met persistence criteria. Authors note possible unmeasured confounding, limited follow‑up due to recent approvals, and potential EMR coding inaccuracies; associations do not establish causality.
Regulatory and safety notes
Semaglutide 2.4 mg has FDA accelerated approval for adults with MASH with moderate‑to‑advanced fibrosis (not cirrhosis) and carries a Boxed Warning for possible thyroid tumors; common adverse effects include gastrointestinal symptoms and other listed events.
Source: Novo Nordisk