SGLT2 inhibitors and incretin-based therapies for metabolic dysfunction-associated steatohepatitis: a systematic review
Abstract
Background: In recent years, metabolic therapies originally developed to treat systemic metabolic disorders have been investigated as potential therapeutic strategies for Metabolic dysfunction-associated steatohepatitis (MASH).
Objective: This study aimed to critically evaluate recent clinical evidence on emerging metabolic therapies, particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors and incretin-based agents, examining their effects on hepatic and metabolic outcomes and, when available, histological endpoints, as well as safety in patients with MASH.
Methods: A systematic review of clinical studies evaluating metabolic therapies in patients with MASH or metabolically associated fatty liver disease was conducted. Randomized clinical trials and other relevant clinical studies investigating SGLT2 inhibitors, incretin-based therapies, and other emerging metabolic agents were included. Outcomes of interest comprised metabolic parameters, hepatic outcomes related to steatosis and disease activity, and histological endpoints when available.
Results: Twelve clinical studies were included. In trials with histological endpoints, semaglutide achieved steatohepatitis resolution without worsening of fibrosis in 62.9% versus 34.3% with placebo in a phase 3 trial (p < 0.001), while a phase 2 trial reported NASH resolution in 59% versus 17% with placebo (p < 0.001), without significant fibrosis improvement (43% versus 33%; p = 0.48). Tirzepatide achieved MASH resolution…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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