TABLE 5.

Mechanism and research progress of combination therapy for NAFLD.

Drug name	Mechanism	NCT number	Current research progress	Status	Reference
Vitamin E and Pioglitazone	Improve inflammation and steatosis	NCT01002547	Phase Ⅳ	Completed	Bril et al. (2019)
Vitamin E and Hydroxytyrosol	Improve oxidative stress, insulin resistance, and steatosis	NCT02842567	Phase Ⅲ	Completed	Mosca et al. (2021)
Pentoxiphylline and Vitamin E	Reduce hepatic inflammation and fibrosis	NCT01384578	Phase Ⅲ	Withdrawn	Kedarisetty et al. (2021)
Tropifexor and Cenicriviroc	Improve fibrosis and steatohepatitis	NCT03517540	phase Ⅱb	Completed	Pedrosa et al. (2020)
Obeticholic acid and atorvastatin	Ameliorate the OCA-induced side effects on plasma lipoprotein spectrum	NCT02633956	Phase Ⅱ	Completed	Pockros et al. (2019)
Cilofexor and Firsocostat	Improve fibrosis	NCT03449446	Phase Ⅱ	Completed	Loomba et al. (2021)
Omega-3 fatty acids and probiotic	Reduce liver fat, improve metabolism and inflammation	NCT03528707	Clinical phase	Completed	Kobyliak et al. (2018)
N-3 fatty acids and phytosterol esters	Improve the efficacy on hepatic steatosis and decrease the levels of inflammation	ChiCTR1800014419	Clinical phase	Completed	Song et al. (2020)
Synbiotic and sitagliptin	Improve the efficacy on steatosis and inflammation of liver	-	Clinical phase	Completed	Sayari et al. (2018)
Vitamin E and Vitamin D and Silybin	Reduce hepatic inflammation and fibrosis	NCT04640324	Clinical phase	Completed	Federico and Dallio, (2019)
Vitamin E, artichoke leaf extract and metformin	Improve inflammation and fat accumulation	IRCT2017040429278N1	Clinical phase	Completed	Majnooni et al. (2021)
Obeticholic acid and elafbranor	Improve the interaction with lipid treatment and insulin signal transduction, inhibit immune response and reduce the formation of extracellular matrix	-	Preclinical study	Completed	Roth et al. (2019)
SUMOylation inhibitors and FXR agonists	SUMOylation inhibitors rescue FXR signaling and thereby increasing the efficacy of OCA against HSC activation and fibrosis	-	Preclinical study	Completed	Zhou and Cui, (2020)
Metformin and genistein	Reduce blood glucose and the level of TG in the liver and affect the pathway of gluconeogenesis	-	Preclinical study	Completed	Zamani-Garmsiri et al. (2021)
Luteolin and lycopene	Improve the cell viability and lipid accumulation of HepG2 cells and primary hepatocytes induced by PA, and improve weight gain and hepatocyte steatosis	-	Preclinical study	Completed	Zhu et al. (2020)
Glucagon-like peptide-1 receptor agonist and obeticholic acid	Reduce liver steatosis, inflammation and fibrosis	-	Preclinical study	Completed	Jouihan et al. (2017)

Sirt1, Sirtuins1; AMPK, AMP-activated protein kinase; TG, triglyceride.