Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes: Pathophysiology, diagnosis, and emerging therapeutic strategies

Table 1 Pharmacologic therapies for metabolic dysfunction-associated steatotic liver disease: Liver fat, cardiometabolic, and fibrosis impact[9,92,160-162]

Drug	Class	Liver effects	CV/metabolic effects	Fibrosis impact	Ref.
Metformin	Biguanide	Unchanged	Improves insulin sensitivity	Neutral	Cusi et al[9]
Pioglitazone	PPAR-γ agonist	Decreased	Improves insulin sensitivity	Improved	Cusi et al[9]
Insulin	Hormone	Decreased	Glucose control	Unknown	Cusi et al[9]
GLP-1 RAs (semaglutide, liraglutide)	GLP-1 RA	Decreased	Weight loss, CV benefit	Improved	Cusi et al[9]; Lin et al[92]
SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin)	SGLT2 inhibitor	Decreased	Weight loss, glycemic control	Effect unknown	Cusi et al[9]
DPP-IV inhibitors (sitagliptin, vildagliptin)	DPP-IV inhibitor	Unchanged (in RCTs)	Modest glucose control	Effect unknown	Cusi et al[9]
Vitamin E	Antioxidant	Not specified	Neutral	Improved (non-diabetics)	Cusi et al[9]
Obeticholic acid	FXR agonist	Not specified	Raises LDL, pruritus	Improved (fibrosis)	Lin et al[92]; Marek and Malhi[161]
Elafibranor	PPAR-α/δ agonist	Not specified	Improves lipids	Improved	Lin et al[160]; Marek and Malhi[161]
Cenicriviroc	CCR2/CCR5 antagonist	Not specified	Neutral	Improved	Lin et al[160]; Marek and Malhi[161]
Aramchol	SCD1 inhibitor	Not specified	Neutral	Improved	Lin et al[160]; Marek and Malhi[161]
Selonsertib	ASK1 inhibitor	Not specified	Neutral	Improved	Marek and Malhi[161]
Resmetirom	THR-β agonist	Not specified	Neutral	Improved	Marek and Malhi[161]
Tirzepatide	GLP-1/GIP RA	Decreased	Weight loss, metabolic improvement	Improved	Handu et al[162]
Survodutide	GLP-1/glucagon RA	Not specified	Weight loss	Improved	Handu et al[162]
FGF-21 analogues	FGF-21 mimetic	Decreased	Improves lipid and glucose metabolism	Improved	Lin et al[160]; Marek and Malhi[161]
THR-β agonists	Thyroid hormone receptor-β agonist	Decreased	Neutral	Improved	Lin et al[160]; Marek and Malhi[161]
Pan-PPAR agonists	Pan-PPAR agonist	Decreased	Improves lipids, insulin sensitivity	Improved	Lin et al[160]; Marek and Malhi[161]
Curcumin	Polyphenol	Not specified	Antioxidant effects	Improved	Handu et al[162]
Silymarin	Flavonoid	Not specified	Hepatoprotective	Improved	Handu et al[162]
Resveratrol	Polyphenol	Not specified	Antioxidant/anti-inflammatory	Improved	Handu et al[162]
Coffee	Dietary	Not specified	Anti-inflammatory, antioxidant	Improved	Handu et al[162]
Green tea	Catechin-rich beverage	Not specified	Anti-inflammatory	Improved	Handu et al[162]
Berberine	Plant alkaloid	Not specified	Improves insulin resistance	Improved	Handu et al[162]

This table summarizes pharmacologic agents studied in the management of metabolic dysfunction-associated steatotic liver disease, detailing their effects on hepatic steatosis, cardiometabolic outcomes, and hepatic fibrosis. It includes both antidiabetic and emerging investigational agents. Reference numbers correspond to clinical trials and major reviews. Therapies such as glucagon-like peptide-1 receptor agonists, peroxisome proliferator-activated receptor agonists, and thyroid hormone receptor-β agonists demonstrate multifaceted benefits, while others remain investigational or population-specific. CV: Cardiovascular; GLP-1 RA: Glucagon-like peptide-1 receptor agonists; DPP: Diabetes prevention program; SGLT2: Sodium-glucose cotransporter 2; THR: Thyroid hormone receptor; FGF: Fibroblast growth factor; PPAR: Peroxisome proliferator-activated receptor; SCD1: Stearoyl-CoA desaturase 1; FXR: Farnesoid X receptor; ASK1: Apoptosis signal-regulating kinase 1; LDL: Low density lipoprotein; RCT: Randomized clinical trial.