. 2021 Apr 20;64(7):1461–1479. doi: 10.1007/s00125-021-05442-2

Table 7.

Drugs that target hepatokines or modulate lipid metabolic pathways

Drug	Mechanism of action	Mode of administration	Regulatory status	Clinical effect					References
Drug	Mechanism of action	Mode of administration	Regulatory status	Steatosis	Fibrosis markers	Hepatic enzymes	HbA_1c	Insulin resistance	References
Hepatokines
Pegbelfermin (BMS-986036)	Long-acting FGF-21 analogue	SC	Phase III	↓	↓	↓	=	=	[114, 115]
BIO89–100	PEG FGF-21 analogue	SC	Phase Ib/IIa	↓	NA	↓	↓	↓	[116]
PF-05231023	Long-acting FGF-21 analogue	SC	Phase II	NA	NA	=	=	=	[117]
PsTag600-FGF21	Long-acting FGF-21 analogue	SC	Preclinical	↓	↓	↓	↓	NA	[118, 119]
NGM313 MK3655	Activator of β-klotho/ FGF receptor-1c	SC once-monthly	Phase I	↓	NA	NA	↓	↓	[121]
Evinacumab (REGN1500)	ANGPLT3 inhibitor	SC	Phase III	NA	NA	=	NA	NA	[123–125]
Hepatic lipid modulators
Aramchol	SCD1 inhibitor	PO	Phase III/IV	↓=	↓	↓	↓	=	[126, 194]
MK-8245	SCD1 inhibitor	PO	Phase II	NA	NA	NA	↓	NA	[195]
PF-06835919	KHK inhibitor	PO	Phase II	↓	NA	↓	NA	↓	[128, 129]
TVB-2640	FAS inhibitor	PO	Phase IIa	↓	NA	↓	=	=	[130]
GSK3008356	DGAT-1 inhibitor	PO	Phase I	NA	NA	NA	NA	NA	[132]
KR-69232	DGAT-1 inhibitor	PO	Phase I	NA	NA	NA	NA	NA	[133]
ION 224 (IONIS DGAT2Rx)	DGAT-2 inhibitor	PO	Phase II	↓	NA	=	=	=	[131]
Epeleuton (DS102)	Second-generation synthetic n-3 fatty acid derivative of EPA	PO	Phase II	↓	=	=	↓	↓	[134]
GS-0976 (firsocostat)	ACC inhibitor	PO	Phase II	↓	↓	↓	=	=	[135, 136]
Thyroid receptor-β agonists
Resmetirom (MGL-3196)	Hepatic thyroid hormone receptor-β agonist	PO	Phase II/III	↓	↓	↓	NA	NA	[137]
VK2809	Hepatic thyroid hormone receptor-β agonist	PO	Phase IIb	↓	NA	↓	=	NA	[139]
11β-HSD1 inhibitors
MK0916	11β-HSD1 inhibitor	PO	Phase I/II	NA	NA	NA	↓modest	↓	[140, 148]
INCB13739	11β-HSD1 inhibitor	PO	Phase I/II	NA	NA	NA	↓	↓	[141, 142]
RO5093151	11β-HSD1 inhibitor	PO	Phase I/II	↓	NA	↓	↓	↓	[143, 144]
ASP3662	11β-HSD1 inhibitor	PO	Phase I/II	NA	NA	NA	NA	NA	[145]
AZD4017	11β-HSD1 inhibitor	PO	Phase I/II	NA	NA	NA	NA	NA	[146, 147]
PTP1B inhibitors
IONIS-PTP-1BRx	PTP1B inhibitor	SC	Phase II	NA	NA	NA	↓	↓	[149]

EPA, eicosapentaenoic acid; PEG, pegylated; PO, oral; SC, subcutaneous injection