survodutide mastery course
Unit 5 of 12

MASH and Liver Disease

from fatty liver to fibrosis: what survodutide does differently

The Liver Disease Opportunity

Metabolic dysfunction-associated steatohepatitis (MASH) affects millions and has limited treatment options. Survodutide's glucagon component drives direct hepatic effects that GLP-1-only agonists cannot match. This unit covers the disease progression, the Phase 2 biopsy data, and the fibrosis resolution signal that earned FDA Breakthrough Therapy designation.

Interactive Liver Pathology

Trace the progression from healthy liver through steatosis, inflammation, and fibrosis.

liver pathology progression

key numbers

quick reference for the Phase 2 MASH trial headline data.

62%
MASH resolution at 4.8 mg (vs 14% placebo)
64.5%
fibrosis improvement (F2-F3) at 6.0 mg
293
patients enrolled in Phase 2 MASH trial
48 weeks
treatment duration (biopsy-confirmed endpoints)
The Phase 2 MASH trial (published NEJM 2024) used histological endpoints requiring paired liver biopsies. These are the gold standard for MASH clinical trials but carry inherent sampling variability. Phase 3 (LIVERAGE) will need to confirm these results in a larger population with 52-week histological assessment.

key terms

liver disease vocabulary for this unit. tap to expand.

M MASLD condition
Metabolic dysfunction-associated steatotic liver disease. The umbrella term for fatty liver caused by metabolic factors rather than alcohol. Affects roughly 30% of the global population. Simple steatosis (fat accumulation >5%) without significant inflammation.
M MASH condition
Metabolic dysfunction-associated steatohepatitis. The progressive form of MASLD with lobular inflammation and hepatocyte ballooning. NAS score of 4 or higher. Carries risk of fibrosis advancement to cirrhosis. Affects roughly 5% of global adults.
N NAS score clinical tool
NAFLD Activity Score. A histological scoring system (0-8) combining steatosis (0-3), lobular inflammation (0-3), and hepatocyte ballooning (0-2). A NAS of 4 or higher with ballooning is used to define MASH in clinical trials.
F fibrosis staging classification
F0 (none), F1 (perisinusoidal or periportal), F2 (perisinusoidal + periportal), F3 (bridging fibrosis), F4 (cirrhosis). Fibrosis stage is the strongest predictor of liver-related mortality. The survodutide Phase 2 trial enrolled F1-F3 patients.
L LIVERAGE trial
Survodutide's Phase 3 MASH trial. Planned enrollment of ~1,400 patients with F2-F3 fibrosis. Dual endpoints: 52-week histological assessment (accelerated approval pathway) plus 7-year clinical outcomes (traditional approval). Largest MASH treatment trial to date.

disease progression

liver disease advances through defined stages. survodutide targets the steatosis-to-fibrosis window where intervention can prevent irreversible damage.

healthy
less than 5% liver fat. no inflammation, no fibrosis (F0).
steatosis (MASLD)
5-33% liver fat. minimal inflammation. F0. reversible. affects ~30% of adults globally.
MASH
over 33% fat with active inflammation and ballooning. NAS 4+. F1-F2. survodutide Phase 2: 62% achieved resolution.
advanced fibrosis
F2-F3, progressive scarring. strongest predictor of liver-related mortality. survodutide: 64.5% improved by at least 1 stage.
cirrhosis
F4, end-stage. regenerative nodules, portal hypertension. largely irreversible. risk of hepatocellular carcinoma.

Phase 2 MASH results at a glance

headline histological outcomes from the 48-week biopsy-confirmed trial (NEJM 2024).

The Phase 2 MASH trial enrolled 293 patients with biopsy-confirmed MASH (F1-F3 fibrosis) and randomized them to survodutide (2.4 mg, 4.8 mg, or 6.0 mg weekly) or placebo. At 48 weeks, MASH resolution without worsening fibrosis was achieved by 62% of patients on the 4.8 mg dose and up to 83% on higher doses, compared to 14% on placebo.

Among patients with more advanced fibrosis (F2-F3), 64.5% on the 6.0 mg dose showed fibrosis improvement by at least one stage, compared to 25.9% on placebo. These results -- published in the New England Journal of Medicine -- were the basis for FDA Breakthrough Therapy designation for MASH with moderate to advanced fibrosis.