Table 1.

Mechanisms and primary outcomes of potential drugs for treating NAFLD.

Drug	Mechanism	Therapeutic Benefits	Side Effects	Clinical No.	Ref.
Metformin	Activating AMPK and inhibiting ACC	Inhibiting adipogenesis and improving IR	Appetite suppression	NCT00736385	[140]
Liraglutide	Activating GLP-1	Improving insulin sensitivity and metabolic disorders	Appetite suppression	NCT01237119	[141]
Statins	Inhibiting HMG-CoA	Reducing plasma total cholesterol and low density lipoprotein	Raised aminotransferases	NCT03434613	[142]
GS-0976	Inhibiting ACC	Reducing triglyceride accumulation in hepatocytes	Nausea and vomiting	NCT03987074	[143]
MGL-3196	Activating THR-β	Improving lipid metabolism and steatosis	Transient diarrhea	NCT04197479	[144]
Vitamin E	Inhibiting ROS	Reducing oxidative stress and inflammation
Obeticholic acid	Activating FXR	Improving lipid metabolism	Pruritus	NCT01265498	[145]
Cilofexor	Activating FXR	Improving inflammation and fibrosis	Pruritus	NCT02654002	[146]
Tropifexor	Activating FXR	Improving adipogenesis, inflammation, and fibrosis	Pruritus and cholestatic disorders	NCT03681457	[147]
Elafibranor	Activating PPARα/δ	Improving inflammation and fibrosis	Pruritus	NCT01694849	[148]
Lanifibranor	Activating PPARα/δ/γ	Improving NASH and liver fibrosis	peripheral edema	NCT03459079	[149]
NGM282	Activating FGF19	Reducing liver fat, liver injury, and inflammation	Nausea and abdominal pain	NCT02443116	[150]
BMS-986036	Activating FGF21	Improving insulin sensitivity, liver fat content, and adiponectin content	Immunogenicity	NCT03486899	[151]
Cenicriviroc	Inhibiting CCR2/CCR5	Improving inflammation and fibrosis	Headache	NCT02330549	[152]
IDN-6556	Inhibiting pan-caspase	Improving apoptosis, inflammation, and fibrosis		NCT02077374	[153]
GR-MD-02	Inhibiting galectin-3	Improving fibrosis		NCT02077374	[154]
Empagliflozin	Inhibiting SGLT-2	Reducing ALT and liver fat	Acute kidney injury		[155]
Canagliflozin	Inhibiting SGLT-2	Improving AST, FIB-4 index	Acute renal failure		[156]
Rosiglitazone	Activating PPAR-γ	Improving steatosis and transaminase levels	Heart failure and peripheral edema		[157]
Pioglitazone	Activating PPAR-γ	Improving steatosis, inflammation, and liver histology	Hypoglycemia and lower limb edema	NCT00063622	[158]
Semaglutide	Activating GLP-1	Reducing body weight and liver enzymes	Nausea and diarrhea	NCT02453711	[159]
Pentoxifylline	Inhibiting TNF-a	Improving liver enzymes and insulin resistance	Nausea and vomiting
JKB-121	Activating TLR-4	Reducing liver fat content	Mild drug-related adverse events	NCT02442687	[160]
Emricasan	Inhibiting caspase	Improving fibrosis	Chest pain and headache	NCT02686762	[134]
Selonsertib	Inhibiting ASK-1	Improving fibrosis and reduction in hepatic decompensation, hepatocellular carcinoma	Mild drug-related adverse events	NCT03053063	[161]
Atorvastatin	Inhibiting HMG-CoA	Reducing steatosis and improving liver density	Autoimmune hepatitis		[162]
Ezetimibe	Decreasing intestinal cholesterol absorption	Improving aminotransferases and hepatocyte ballooning	New-onset diabetes and increased HbA1c levels		[163]
GS-9674	Activating FXR	Reducing hepatic fat and improving liver biochemistry		NCT02854605	[164]
Aramchol	Inhibiting SCD-1	Reducing liver fat, Ballooning, and AST		NCT04104321	[165]
Losartan	Activating TGF-β	Improving serum aminotransferases and histologic outcomes	Angioedema		[166]
Telmisartan	Inhibiting CCR2 and CCR5	Reducing serum ALT levels and improving insulin sensitivity steatosis	Angioedema	NCT01088295	[167,168]
VK-2809	Activating thyroid receptor β	Reducing fat in liver			[144]
Simtuzumab	Monoclonal antibody of LOXL2	Improving liver cirrhosis		NCT01672866	[152]