Quick glance at 'metabolic dysfunction associated steatotic liver disease' therapeutics: Targets, trials, and trends

Table 1 Pharamacotherapy of metabolic dysfunction-associated steatotic liver disease

Class of medication	Mechanism of action/target(s)		Candidate medication	Phase of development notable trials
FXR agonists	Regulates bile acid metabolism; Reduces insulin resistance; Reduces hepatic lipogenesis, inflammation, fibrosis		Obeticholic acid	Phase 3 (REGENERATE)
			Tropifexor	Phase 2 (FLIGHTFXR)
			Cilofexor	Phase 2
PPAR agonists	Increased clearance of intrahepatic fat; Improves insulin sensitivity; Downregulates stellate cells; Attenuates fibrogenesis	Pan PPAR-α/δ/γ	Lanifibranor	Phase 3 (NATiV3)
		Dual PPAR-α/δ	Elafibranor	Phase 3 (RESOLVE-IT)
		Dual PPAR-α/γ	Saroglitazar	Phase 2b
THR-βagonists	Reduce hepatic triglycerides by enhanced intrahepatic lipolysis, lipophagy, β-oxidation, and bile acid synthesis		Resmetirom	Phase 3 (MAESTRO-NASH)
			VK2809	Phase 2b (VOYAGE)
GLP-1 agonists	Induces satiety, weight loss; Incretin effect: Improved glycemic control; Positive effects lipid metabolism		Semaglutide	Phase 3 (ESSENCE)
			Liraglutide	Phase 2 (LEAN)
SGLT2 inhibitors	Improves glycemic control, lipid profile; Weight loss; Postulated anti-inflammatory/antifibrotic effects		Dapagliflozin	Phase 3 (DEAN), Phase 4
			Empagliflozin	Phase 4
Galectin-3 inhibitors	Reduce macrophage-mediated inflammation; Inhibits activation and proliferation of stellate cells; Reduces hepatocyte apoptosis, promotes regeneration		Belapectin	Phase 3 (NAVIGATE)
			Selvigaltin	Phase 1b/2a (GULLIVER-2)
FGF analogues	Decreases hepatic fat content; Improves insulin sensitivity; Anti-inflammatory, antifibtotic effects	FGF21	Pegbelfermin	Phase 2b
		FGF19	Aldafermin	Phase 2b (ALPINE)
ACC inhibitors	Decreses de novo lipogenesis; Promotes fatty acid oxidation		Firsocostat	Phase 2
MPC inhibitors	Inhibits pyruate transport from cytosol to mitocondria		MSDC-0602K	Phase 2b (EMMINENCE)
	Decreases de novo lipogeneis, Increases fatty acid oxidation		PXL065	Phase 2 (DESTINY-1)
CCR2/CCR5 antagonist	Anti-inflammatory, antifibrotic effects		Cenicriviroc	Phase 3 (AURORA)
Cyclophiphin inhibitor	Regulates collagen and extracellular matrix; Antisteatotic, anti-inflammatory, antifibrotic effects		Rencofilstat	Phase 2b (ASCEND-NASH)
Pan-caspase inhibitor	Anti-apoptotic, anti-inflammatory effects		Emricasan	Phase 2 (ENCORE-NF)
SCD1 inhibitor	Prevents hepatic triglyceride synthesis		Aramchol	Phase 3 (ARMOR)
LOXL2 inhibitor	Impedes collagen cross linking, fibrosis progression		Simtuzumab	Phase 2
siRNA	Silencing effects of interfering RNA on metabolic pathways, inflammation, callagen synthesis, fibrosis, etc.		GalNAc-siPLIN2	Preclinical
			ALN-HSD	Phase 1/2
			BMS986263	Phase 2
FASN inhibitor	Inhibits de novo hepatic lipogenesis		Denifanstat	Phase 2b (FASCINATE-2)
Vitamin E	Antioxidant action: Reduces hepatic oxidative stress/injury		Vitamin E	Phase 3 (PIVENS; TONIC)
Statins	HMG-CoA reductase inhibitor - blocks cholestrol biosynthesis; Pleomorphic effects: Anti-inflammatory, antifibtotic		Atorvastatin	Phase 2/3