MASLD in obesity should include liver risk stratification

The article argues that liver risk stratification should be part of obesity care and notes that phase 3 ESSENCE results showed semaglutide led to higher rates of MASH resolution and fibrosis improvement, supporting FDA accelerated approval in August 2025.

The article responds to a proposed pharmacological framework for treating obesity by stressing that metabolic liver disease (MASLD and MASH) must be considered within that approach. It emphasizes the need for liver risk stratification when treating people with obesity because of the close links between obesity, diabetes and liver disease. The authors note that MASH has become a rapidly growing indication for liver transplantation, which increases the urgency for accurate guidance. They also review recent clinical-trial evidence relevant to drug choices for MASH. Key facts: - A phase 2b trial of semaglutide in MASH reported MASH resolution without worsening fibrosis in 59% of participants versus 17% with placebo, although fibrosis improvement did not reach statistical significance. - The phase 3 ESSENCE trial (800 biopsy-confirmed participants; 534 on semaglutide, 266 on placebo) reported semaglutide 2.4 mg achieved MASH resolution without fibrosis worsening in 62.9% versus 34.3% with placebo, and ≥1-stage fibrosis improvement without MASH worsening in 36.8% versus 22.4% with placebo; top-line results were released on 1 November 2024. - Those ESSENCE findings provided the basis for FDA accelerated approval of semaglutide for non-cirrhotic MASH with F2–F3 fibrosis in August 2025. - By contrast, tirzepatide’s evidence in MASH is currently limited to a small phase 2b SYNERGY-NASH trial with fewer than 50 patients per active arm and lacks confirmatory phase 3 data. Summary: The authors call for routine liver risk stratification as part of obesity management given rising MASH-related transplant needs, and they point to phase 2 and phase 3 semaglutide data that informed regulatory action. The evidence base for alternative agents such as tirzepatide is smaller at present, and confirmatory phase 3 results are undetermined at this time.