Table 2.

Selected clinical trials of mitochondria-centric drugs

Drug	Author (year)	National Clinical Trial numbers	Mechanism of action	Study outcomes
				Liver enzymes	Histology
Vitamin E	Sanyal et al. (2010)86	NCT00063622 NCT02690792 NCT01792115 NCT02962297 NCT04198805 NCT01147523 NCT01934777 NCT00655018	Restoration the hepatic glutathione level	Improved	Improved steatosis and inflammation
Metformin	Loomba et al. (2009)87	NCT00063232 NCT00736385 NCT02696941 NCT05521633	Activation of AMPK signaling	Improved	Improved parenchymal inflammation and cellular injury
Resveratrol	Faghihzadeh et al. (2014)93	NCT01446276 NCT02030977 NCT01464801 NCT02216552	Activation of mitochondrial biogenesis and mitochondria-located antioxidant enzymes	Improved	Improved hepatic steatosis
Betaine	Abdelmalek et al. (2009)88	NCT00586911 NCT03073343	Restoration of hepatic mitochondrial glutathione and S-adenosyl methionine	No improvement	Improved hepatic steatosis
Pentoxifylline	Zein et al. (2011)89	NCT00267670 NCT00590161 NCT05284448	Increasing Nrf2 and PGC-1α through the cAMP–CREB pathway	No improvement	Improved steatosis, inflammation, and fibrosis
Liraglutide	Armstrong et al. (2016)90	NCT02147925 NCT03068065 NCT01399645 NCT03233178 NCT01237119 NCT05041673 NCT05779644 NCT02654665	Enhancing mitochondrial architecture through the SIRT1/SIRT3 signaling	Improved	Improved hepatic steatosis
Exenatide	Liu et al. (2021)91	NCT02303730 NCT01006889 NCT01208649 NCT00650546 NCT00529204	Enhancing mitochondrial architecture through the SIRT1/SIRT3 signaling	Improved	Improved hepatic steatosis
Semaglutide	Newsome et al. (2021)92	NCT02970942	Enhancing mitochondrial architecture through the SIRT1/SIRT3 signaling	Improved	Improved hepatic fibrosis and reduced liver-enzyme levels

AMPK, AMP-activated protein kinase; Nrf2, nuclear factor erythroid 2-related factor 2; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; cAMP, cyclic adenosine monophosphate; CREB, cAMP-response element binding protein; SIRT1, sirtuin 1; SIRT3, sirtuin 3.