Conditional US approval of resmetirom and semaglutide gave clinicians, for the first time, pharmacological therapy for metabolic dysfunction-associated steatohepatitis with significant fibrosis (F2-F3) and no cirrhosis. This international expert panel review consolidates the phase 3 data, the FDA labels and early clinical experience into a single pathway.
The two agents work differently and the panel treats that as the basis for selection. Resmetirom is a liver-directed thyroid hormone receptor-beta agonist; semaglutide is a GLP-1 receptor agonist with broad metabolic effects. The review covers non-invasive test-based diagnosis of MASH with significant fibrosis, treatment selection and initiation, on-treatment monitoring, and — the part most often missing from a new-drug guideline — how to define response and non-response, and when to switch or combine.
It also addresses the situation many clinicians are already in: a patient with MASH already taking a GLP-1 receptor agonist for obesity or diabetes. That patient does not need a new prescription so much as a decision about whether the existing one is doing the liver work. The panel is explicit that the framework will change as long-term outcome data arrive — both approvals are conditional, and neither drug has yet shown a reduction in hard liver outcomes.
- Diagnose F2-F3 fibrosis with non-invasive tests before prescribing; neither drug is licensed for cirrhosis or for steatosis without significant fibrosis.
- Check whether a patient with MASH is already on a GLP-1 receptor agonist before adding a second agent.
- Define what response means at the point of starting, and set the interval at which you will assess it.
- Say plainly that both approvals are conditional and neither has yet shown a reduction in cirrhosis, decompensation or death.
- Neither agent is widely available or affordable in Indian practice; weight loss, metabolic control and alcohol avoidance remain the interventions that are.
Why it matters
Two drugs arrived for a disease that had none, and the harder question is now which patient, which agent and when to stop.
Don't overread it
Both approvals are conditional and based on histological endpoints; neither drug has yet demonstrated fewer liver-related events or deaths.
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