GLP-1 RAs may become an established MASH (metabolic dysfunction-associated steatohepatitis) therapy. SYNERGY-NASH (tirzepatide) showed MASH resolution 44–62% at 52 weeks. ESSENCE (semaglutide 2.4 mg) phase 3 interim May 2026 showed ~62% MASH resolution at 72 weeks. Plausible 2027 FDA indication for both.
The evidence
SYNERGY-NASH (NEJM 2024): tirzepatide 5/10/15 mg vs placebo in F2-F3 fibrosis MASH. MASH resolution: 44%, 56%, 62% by dose vs 10% placebo at 52 weeks. ESSENCE (NEJM 2026, interim): semaglutide 2.4 mg in F2-F3 MASH; ~62% MASH resolution at 72 weeks.
FDA-approved labeling status
No GLP-1 RA currently has an FDA-approved MASH indication. Phase 3 programs advancing — plausible 2027 indications for both sema and tirz based on interim/final readouts.
Practical considerations
Patients with biopsy-confirmed MASH and F2-F3 fibrosis are the population studied. Hepatology coordination is essential. Compounded GLP-1 for MASH-specific intent is off-label even by editorial framing.