Emerging treatment options for metabolic dysfunction-associated steatotic liver disease and its related liver diseases

Table 1 Treatment of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis in clinical trials

Clinical trials	Phase	Treatments	Effects	Ref.
NCT05006885	1	Pemvidutide (also known as ALT-801), a GLP-1/glucagon dual receptor agonist	Reduction in body weight Reduction in ALT levels Decrease in liver corrected T1	[65]
NCT05090111	1	ALG-055009, an oral THR-β agonist	Decrease in atherogenic lipids in a dose-dependent manner. Increase in sex hormone-binding globulin	[66]
NCT06491576	1/2	BGT-002, an ATP-citrate lyase inhibitor	Reduction in circulating GGT levels	[68]
NCT04202354	1/2	GSK4532990 (ARO-HSD), an RNA interference targeting HSD17β13 mRNA in hepatocytes	Reduction in hepatic HSD17β13 mRNA and protein expression, as well as alanine aminotransferase	[69]
NCT05989711	2	Pemvidutide	Improvement in MASH resolution, without worsening liver fibrosis	[70]
NCT04166773	2	Tirzepatide, a dual GLP-1 and GIP receptor agonist	Reduction in body weight, HbA1c, with improvement of liver fibrosis	[72]
NCT04771273	2	Survodutide, a dual agonist of glucagon receptor and GLP-1 receptor	Improvement in MASH resolution without worsening of fibrosis	[73]
NCT04881760	2	Retatrutide, a novel triple agonist of the GIP, GLP-1, and glucagon receptors	A reduction in liver fat compared to placebo in a dose-dependent manner	[74]
NCT03656744	2	Berberine ursodeoxycholate (HTD1801), an ionic salt of berberine and ursodeoxycholic acid	Improved glycemic control and reduced body weight, liver fat content, and serum ALT and GGT levels	[76]
NCT02413372 NCT04929483	2	Pegbelfermin (BMS-986036), a PEGylated human FGF21 analogue	Decrease in hepatic fat fraction Improvement in liver fibrosis	[77,78]
NCT04210245	2	Aldafermin, an engineered human hormone FGF19 analogue	Reduction in liver fibrosis	[79]
NCT03459079	2	Lanifibranor, a pan-peroxisome proliferator-activated receptor agonist	Improvement in liver inflammation and fibrosis. Decrease hepatic fat accumulation	[80]
NCT04906421	2	Denifanstat, an oral fatty acid synthase inhibitor	Improvement in MASLD activity score without worsening fibrosis. Improvement in MASH resolution	[81]
CTRI/2023/08/0559821	3	24-norursodeoxycholic acid	Reduction in ALT levels. Improvement in liver fibrosis and stiffness	[83]
NCT03723252	3	Dapagliflozin, a SGLT inhibitor	Improvement in fibrosis and MASH resolution	[85]
NCT05647915	4	Berberine plus lifestyle intervention	Decrease in LDL cholesterol, apolipoprotein B, and hs-CRP levels	[88]

¹Clinical Trials Registry-India.

ALT: Alanine aminotransferase; FGF: Fibroblast growth factor; GGT: Gamma-glutamyl transferase; GGT: Gamma-glutamyl transferase; GIP: Glucose-dependent insulinotropic polypeptide; GLP-1: Glucagon-like peptide-1; hs-CRP: High-sensitivity C-reactive protein; HSD17β13: Hydroxysteroid 17-beta dehydrogenase 13; LDL: Low-density lipoprotein; SGLT2: Sodium-glucose co-transporter 2; THR-β: Thyroid hormone receptor beta; MASLD: Metabolic dysfunction-associated steatotic liver disease; MASH: Metabolic dysfunction-associated steatohepatitis.

Table 2 Next-generation therapies for metabolic dysfunction-associated steatotic liver disease

Clinical trials	Phase	Treatments	Effects	Ref.
NCT04555434	N/A	Probiotics	Decrease in ALT and AST levels, body weight, and cholesterol levels by regulating gut microbial components	[89]
NCT04527965	N/A	A low-carbohydrate PUFA diet or a low-fat HND	Decrease in liver fat accumulation and LDL cholesterol levels in both diets. HND intervention further decreases body weight, ALT, AST, triglycerides, CRP, and HbA1c levels	[90]
NCT06220695	N/A	Isocaloric Mediterranean diet and low-fat diet	Decrease in body weight, hepatic steatosis, and fibrosis	[91]
NCT03118310	2	5:2 diet low-carb high-fat	Decrease in body mass index, hepatic steatosis, and liver stiffness	[92]
PACTR2022065315457291	2	Phenolic acid fraction	Improvement in hepatic steatosis. Decrease in fasting triglycerides, non-HDL cholesterol, ALT, and AST levels	[96]
IRCT20180103038199N162	N/A	Ellagic acid, a polyphenol	Improvement in liver stiffness. Decrease in levels of ALT, AST, fasting blood sugar, triglycerides, and LDL cholesterols	[97]
NCT07211113	N/A	Fonte Essenziale®, a mineral water	Decrease in serum markers of liver injury, hepatic steatosis, systemic inflammation. Improvement in intestinal permeability	[98]
NCT04142424; NCT04483947	1	AZD2693, a liver-targeted antisense oligonucleotide against PNPLA3 mRNA	Improvement in hepatic steatosis. Decrease in hs-CRP and IL-6	[101]
NCT06025851; NCT06037577; NCT06044467	1	Anti-human CCL24 monoclonal antibody (CM-101)	Decrease in serum levels of inflammatory and fibrotic biomarkers	[102]

¹Pan African Clinical Trials Registry.

²Iranian Registration of Clinical Trials.

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LDL: Low-density lipoprotein; HbA1c: Hemoglobin A1c; HDL: High-density lipoprotein; hs-CRP: High-sensitivity C-reactive protein; IL: Interleukin; mRNA: Messenger ribonucleic acid; N/A: Not applicable; PNPLA3: Patatin-like phospholipase domain-containing protein 3; PUFA: Polyunsaturated fatty acids; HND: Healthy Nordic diet.

Table 3 Strategies to improve metabolic dysfunction-associated steatotic liver disease treatment

Clinical trials	Phase	Treatments	Effects	Ref.
NCT03183193	N/A	Dietary intervention	Modulation of circulating miRNAs	[105]
NCT03008070	2	Serum biomarkers	Providing a non-invasive test for evaluating the treatment response to lanifibranor	[107]
NCT03151798	N/A	Lifestyle change: Energy restriction and exercise	Decrease in body weight, fat mass, liver fat accumulation, and insulin resistance	[108]
NCT05866744	N/A	Time-restricted feeding	Improvement in insulin resistance. Decrease in HbA1c	[109]
DRKS000247061	N/A	Artichoke leaf extract	Decrease in hepatic fat accumulation and liver size	[110]
NCT03426111	N/A	Endoscopic sleeve gastroplasty	Decrease in body weight, liver stiffness, and hepatic steatosis	[111]
NCT03646292	4	Pioglitazone and empagliflozin	Reduction in hepatic fat, liver stiffness, and visceral fat	[113]

¹German Clinical Trials Register.

HbA1c: Hemoglobin A1c; N/A: Not applicable.