GLP-1, GIP/GLP-1, and GCGR/GLP-1 receptor agonists: Novel therapeutic agents for metabolic dysfunction-associated steatohepatitis

Table 1 GLP-1 agonist and their demonstrated effects on Metabolic-associated steatohepatitis and liver fibrosis

Drug	Mechanism of action	Method of testing	Effect on MASH	Effect on fibrosis
Liraglutide[24]	GLP-1 RA	Biopsy	Improvement in MASH with no worsening of fibrosis; Liraglutide 18 mg–resolution in 39%; Placebo-resolution in 9%	Improvement in fibrosis stage: liraglutide 6 (26%) vs Placebo 3 (14%) (RR = 1.9, 95%CI: 0.5-6.7; P = 0.46)
				Worsening of Fibrosis stage: liraglutide 2 (9%) vs Placebo 8 (36%) [RR = 0.2 (95%CI: 0.1-1; P = 0.04)]
Semaglutide[26]	GLP-1 RA	Biopsy	Improvement in MASH with no worsening of fibrosis	Improvement of at least one stage of fibrosis with no worsening of MASH: (1) Semaglutide 0.1 mg-49%; (2) Semaglutide 0.2 mg-32%; (3) Semaglutide 0.4 mg-43%; and (4) Placebo-33% (none were statistically significant); Worsening of Fibrosis stage: (1) Semaglutide 0.1 mg-10%; (2) Semaglutide 0.2 mg-8%; (3) Semaglutide 0.4 mg-5%; and (4) Placebo-19%
			Semaglutide 0.1 mg-resolution in 40% patients
			Semaglutide 0.2 mg-resolution in 36%
			Semaglutide 0.4 mg-resolution in 59%
			Placebo-resolution in 17%
Tirzepatide[27]	GLP-1/GIP RA	Biopsy	Improvement in MASH with no worsening of fibrosis: Tirzepatide 5 mg-resolution in 44%; Tirzepatide 10 mg-resolution in 56%; Tirzepatide 15 mg-resolution in 62%; Placebo-resolution in 10%	Improvement of at least one stage of fibrosis: (1) Tirzepatide 5 mg-55%; (2) Tirzepatide 10 mg-51%; (3) Tirzepatide 15 mg-51%; (4) Placebo-30%
Survodutide[30]	GCGR/GLP-1 RA	Biopsy	Improvement in MASH with no worsening of fibrosis: Survodutide 2.4 mg-47%; Survodutide 4.8 mg-62%; Survodutide 6 mg–in 43%; Placebo-14%	Improvement of alteast one stage of fibrosis: (1) Survodutide 2.4 mg-34%; (2) Survodutide 4.8 mg-36%; and (3) Survodutide 6 mg-34%; and (4) Placebo-22%
Efinopegdutide[31]	GCGR-1/GLP-1 RA	MRI-PDFF	The least squares mean relative reduction in LFC: Efinopegdutide 10 mg-72.7%; Semaglutide 1 mg-42.3%	No data available
Pemvidutide[32]	GCGR/GLP-1 RA	MRI-PDFF	Absoluted reduction in LFC: Pemvidutide at 1.2 mg-8.9%; Pemvidutide 1.8 mg-14.7%; Pemvidutide 2.4 mg-11.3%; Placebo-4.4%	No data available

MASH: Metabolic-associated steatohepatitis; LFC: Liver fat content; Glucagon RA: Glucagon receptor agonist; MRI-PDFF: Magnetic resonance imaging-proton density fat fraction.