Relation between cortisol and metabolic dysfunction-associated steatotic liver disease: A dog chasing its tail

Table 2 List of preclinical studies and trial involving 11β-hydroxysteroid dehydrogenase type 1

Compound	Study type	Subjects	Key findings related to liver	Potential indication	Ref.
J2H-1702	Preclinical study	Mice (high fat/high carbohydrate fed)	Decreased triglyceride levels in the liver	MASLD	[82]
INU-101	Preclinical study	Mice (fast-food diet model)	Reduced hepatic lipid accumulation and fibrosis	MASLD and liver fibrosis	[43]
J2H-1702	Preclinical study	Mice (NASH models)	Reduced lipid accumulation and fibrosis	MASH	[41]
BVT2733	Preclinical study	Mice (high fat diet)	Decrease in body weight, better glucose tolerance, reduced inflammation	Obesity-related liver disease	[83]
AZD6925	Preclinical study	Mice	Prevented hepatic steatosis and reduced liver triglycerides levels	MASLD	[84]
BI 135585	Single-dose study and double blind, placebo controlled clinical trial	Healthy volunteers (single dose) and patients with type 2 diabetes	Demonstrated liver 11β-HSD1 inhibition	MASLD in T2D	[85]
BI 187004	Randomized, double-blind, placebo-controlled	Patients with T2D and obesity	Near-full liver 11β-HSD1 inhibition	Liver-related metabolic disorders	[86]
J2H-1702	Randomized, double blinded, placebo-controlled trial	Healthy volunteers	Effectively reduced 11β-HSD1 activity	NASH	[87]
RO5093151	Phase 1b trial. Multicenter, randomized, double-blind, placebo-controlled trial	MASLD patients	Significantly reduced liver-fat content vs placebo	MASLD	[88]
AZD4017	Phase II, randomized, double-blind, placebo-controlled study	NASH or MASLD patients	Reduced conversion of cortisone to cortisol. Able to find a significant difference in reduction of liver fat fraction only in patients with NASH and T2D	MASH with T2D	[48]

MASLD: Metabolic dysfunction-associated steatotic liver disease; NASH: Non-alcoholic steatohepatitis; MASH: Metabolic dysfunction associated steatohepatitis; 11β-HSD1: 11β-hydroxysteroid dehydrogenase type 1; T2D: Type 2 diabetes.