Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review

Table 2 Efficacy and hepatic outcomes of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease

Class	Drug	ALT	GGT	Histological improvement	Effect on fibrosis	MASLD-specific efficacy	Safety profile	Approval (FDA/EMA)
GLP-1 RAs	Liraglutide	Decrease	Decrease	NASH resolution (LEAN trial)	No significant improvement	Histological and biochemical improvement in NASH patients	GI side effects; contraindicated in MTC or gastroparesis	Approved
GLP-1 RAs	Semaglutide	Decrease	Decrease	Steatohepatitis resolution (2021 phase 2)	No fibrosis improvement	Decrease hepatic fat and steatohepatitis resolution	Well tolerated; GI effects most common	Approved
Dual GLP-1/GIP agonist	Tirzepatide	Decrease	Decrease	No biopsy data	Not assessed	Decrease liver fat (MRI-PDFF); improved insulin sensitivity	GI symptoms; minimal hypoglycemia	FDA approved
Triple GLP-1/GIP/glucagon agonist	Retatrutide	Decrease	Decrease	No biopsy data	Not assessed	Decrease marked in hepatic fat in early-phase studies	GI adverse events; not tested in cirrhotics	Investigational
FGF-21 analog	Efruxifermin	Decrease	Decrease	↓Steatosis and ballooning (phase 2 MASH)	Yes (F2-F3 patients)	Biopsy-confirmed improvement in steatosis and fibrosis	Well tolerated; long-term safety under investigation	Investigational
CNS agent	Phentermine/topiramate	Unclear	Unclear	None	None	Presumed via weight loss; no liver-specific trials	Neurocognitive side effects; teratogenicity	Approved (for obesity)
CNS agent	Naltrexone/bupropion	Unclear	Unclear	None	None	No liver-specific data	Neuropsychiatric side effects; caution in seizures	Approved (for obesity)

Summary of drug-specific effects on hepatic biomarkers, histological outcomes, and safety profiles. ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; MASLD: Metabolic dysfunction-associated steatotic liver disease; FDA: Food and Drug Administration; EMA: European Medicines Agency; GLP-1 RAs: Glucagon-like peptide-1 receptor agonists; GLP-1: Glucagon-like peptide-1; FGF-21: Fibroblast growth factor 21; CNS: Central nervous system; NASH: Non-alcoholic steatohepatitis; LEAN: Liraglutide efficacy and action in non-alcoholic steatohepatitis; MASH: Metabolic dysfunction-associated steatohepatitis; MRI: Magnetic resonance imaging; PDFF: Proton density fat fraction; GI: Gastrointestinal; MTC: Medullary thyroid carcinoma.