MASH remains a semaglutide-only indication among GLP-1 drugs

Fourteen months after the FDA approved Wegovy (semaglutide) for metabolic dysfunction-associated steatohepatitis, or MASH, it remains the only GLP-1 receptor agonist with that indication on its label ^[1][2]. Tirzepatide, sold as Mounjaro and Zepbound, has posted stronger early results in a smaller study, but that drug is still in phase 3 testing for liver disease, so any use for MASH today is off-label ^[1].

The FDA approved Wegovy for MASH in August 2025, covering adults with non-cirrhotic MASH and moderate-to-advanced liver scarring, known as fibrosis stage F2 or F3 ^[1][2]. The agency estimates roughly 6% of U.S. adults, or about 14.9 million people, have MASH, and the condition can progress to cirrhosis, liver cancer, liver transplant, or death ^[2]. The approval was based on the ESSENCE trial, which found that 62.9% of people on semaglutide had MASH resolution without worsening fibrosis at 72 weeks, compared with 34.3% on placebo. On the trial's other main measure, 36.8% of the semaglutide group had at least one stage of fibrosis improvement without worsening MASH, versus 22.4% on placebo ^[1][2].

The FDA granted the approval under its accelerated pathway, meaning it is based on liver biopsy results (a surrogate measure) rather than confirmed proof yet that patients live longer or avoid liver transplants ^[1][2]. The ESSENCE trial is continuing for 240 weeks total to see whether the biopsy improvements seen at 72 weeks actually translate into fewer deaths, transplants, and other liver complications ^[2]. The approval also excludes patients who already have cirrhosis, since the trial did not enroll people at that stage ^[1][2]. Notably, when Novo Nordisk added an oral Wegovy tablet to the market in June 2026, that pill version was approved only for weight management and cardiovascular risk reduction — not for MASH, since the liver trial tested the injectable form only ^[1].

Tirzepatide's data come from a smaller, earlier-stage study called SYNERGY-NASH. In that phase 2 trial, the 15 mg dose of tirzepatide produced MASH resolution in 73.3% of participants — a higher rate than semaglutide's 62.9% in ESSENCE, though the two trials were not run head-to-head and differ in size and design ^[1]. Tirzepatide's manufacturer has moved the drug into phase 3 testing for MASH, but until that larger trial reads out and the FDA reviews it, Mounjaro and Zepbound cannot carry a MASH indication, and any use for that purpose is off-label ^[1].

Why it matters for patients

For patients with biopsy-confirmed MASH and moderate-to-advanced fibrosis, Wegovy is currently the only GLP-1 drug that insurers and prescribers can point to with an FDA-approved indication for liver disease specifically, rather than for weight loss alone ^[1][2]. That distinction can matter for insurance coverage decisions, since off-label prescribing of tirzepatide products for liver disease is not backed by the same regulatory review, even though its early trial numbers look promising ^[1].

Patients considering either drug for liver health should know that the labeled MASH use applies only to a specific population: adults with confirmed MASH, fibrosis stage F2 or F3, and no cirrhosis ^[1][2]. People with earlier-stage or no fibrosis, or with existing cirrhosis, fall outside what either the ESSENCE trial or the FDA approval covered. It is not yet known whether tirzepatide will ultimately show similar or better outcomes at the phase 3 level, or how regulators will weigh its results once that trial is complete ^[1].

What happens next

The ESSENCE trial is set to run through 240 weeks to confirm whether Wegovy's liver biopsy improvements lead to fewer real-world outcomes like transplants or liver-related deaths, a requirement of its accelerated approval ^[2]. Tirzepatide's phase 3 MASH trial is ongoing as of September 2026, with no confirmed date in these sources for when results or an FDA filing might arrive ^[1].