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

Table 1 Overview of anti-obesity drug classes, mechanisms of action, and weight loss effects in metabolic dysfunction-associated steatotic liver disease

Class	Drug	Dosage	Mechanism of action	Effect on body weight
GLP-1 RAs	Liraglutide	3.0 mg/day	GLP-1 receptor activation: Satiety, gastric emptying (↓)	8%-10%
GLP-1 RAs	Semaglutide	2.4 mg/week	GLP-1 receptor activation: Satiety, gastric emptying (↓)	10%-15%
Dual GLP-1/GIP agonists	Tirzepatide	5-15 mg/week	Combined GLP-1 and GIP receptor agonism	15%-20%
Triple GLP-1/GIP/glucagon agonists	Retatrutide	8-12 mg/week (in trials)	GLP-1, GIP, and glucagon receptor agonist	Up to 24%
FGF-21 analogs	Efruxifermin	28-70 mg/week (in trials)	FGF21 receptor agonist	Approximately 10%
CNS agents	Phentermine/topiramate	7.5/46 mg/day to 15/92 mg/day	Central appetite suppression via sympathomimetic + GABA modulation	7%-9%
CNS agents	Naltrexone/bupropion	8/90 mg BID	Opioid antagonist and dopamine/norepinephrine reuptake inhibitor	5%-6%

This table summarizes pharmacologic agents currently used or under investigation for weight management in patients with metabolic dysfunction-associated steatotic liver disease. It includes the drug class, name, dosage range, primary mechanism of action, and average weight loss percentages reported in clinical trials. This table supports treatment individualization based on therapeutic goals. GLP-1 RAs: Glucagon-like peptide-1 receptor agonists; GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent insulinotropic polypeptide; FGF-21: Fibroblast growth factor 21; CNS: Central nervous system; BID: Twice daily; GABA: Gamma-aminobutyric acid.

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.