Investigational new drug approval of DA-1241: what we know about GPR119 targeting for MASH therapy?

Figures & data

Table 1. Drugs tested in MASH treatment.

Mechanism of action	Drug	Duration of Treatment	Key Results	Trial Name/Study phase
Antioxidant	Vitamin E	96 weeks	Decrease liver steatosis without change in fibrosis	PIVENs
Antioxidant	Omega-3 fatty acids	18 months	No significant change in liver fibrosis	WELCOME
GLP-1 agonist	Semeglutide	48 months	No significant change in liver fibrosis	Semeglutide phase 2 clinical trial
Activating FXR receptor	Obeticholic acid	18 months	Improved fibrosis, had adverse events	REGENERATE/ongoing
ASK-1 inhibitor	Selonsertib	48 weeks	No significant change in liver fibrosis	STELLAR
THB receptor agonist	Resmetirom	52 weeks	Improved liver fibrosis with at least one stage	MAESTRO-NASH

Figure 1. GPR119 signaling pathways in various tissues

Abbreviations: ABCA1, ATP-binding cassette subfamily A1; ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; CB1, cannabinoid receptor type 1; CPT1, carnitine palmitoyltransferase-1; CTGF, connective tissue growth factor; FAS, fatty acid synthase; GIP, glucose-dependent insulinotropic peptide; GLP-1, glucagon-like peptide-1; Gαs, stimulatory G protein α-subunit; NFATc1, nuclear factor of activated T cells, cytoplasmic 1; OEA, oleoylethanolamide; Ox-LDL, oxidized low-density lipoprotein; PDK4, pyruvate dehydrogenase kinase isozyme 4; PGC1α, peroxisome proliferator-activated receptor-α coactivator 1-α; PKA, protein kinase A; PPARα, peroxisome proliferator-activated receptor-α; SCD1, stearoyl-CoA desaturase-1; SREBP-1, sterol regulatory element binding protein-1.

Figure referenced from Therapeutic application of GPR119 ligands in metabolic disorders (Yang et al.)[1.2]. Reprinted with permission from John Wiley and Sons. © 2017 John Wiley and Sons.