Table 3.

Main evidences on the effect of GLP-1 RA on liver steatosis.

Year	First Author	Ref.	Sample Size	Study Typology	Evaluated Drugs	Benefit	Results
2009	Jendle	[86]	314 uncontrolled T2DM patients	Randomized, double-blind, parallel-group	Metformin + Liraglutide (0.6, 1.2 or 1.8 mg/day) or glimepiride or placebo	Yes	Liraglutide (with or without metformin) significantly reduced fat mass and fat percentage vs glimepiride
2011	Sathyanarayana	[71]	21 T2DM patients	NS	Exenatide vs pioglitazone	Yes	The addition of exenatide to pioglitazone is associated with a greater reduction in hepatic fat content as compared to pioglitazone monotherapy
2012	Cuthbertson	[87]	25 obese, T2DM and NAFLD patients	Prospective single arm	Exenatide	Yes	Exenatide significantly decreased liver fat (evaluated by MR)
2014	Braslov	[74]	125 T2DM patients	Open label parallel-group uncontrolled	Exenatide vs other oral hypoglycaemic agents	Yes	Exenatide induces greater improvement in FLI than other oral hypoglycaemic agents
2015	Tang	[85]	35 uncontrolled T2DM patients	RCT	Liraglutide vs insulin glargine	No	Twelve-week liraglutide treatment liraglutide does not modify liver proton density fat fraction
2015	Eguchi	[76]	19 NASH patients	Prospective uncontrolled	Liraglutide	Yes	Liraglutide significantly improved histological features in NASH
2016	Dutour	[88]	44 obese T2DM patients	RCT	Exenatide vs other hypoglycaemics	Yes	Exenatide induced a significant reduction in hepatic triglyceride content compared with the reference treatment
2016	Smits	[84]	52 overweight T2DM patients	Randomised, placebo-controlled	Liraglutide 1.8 mg vs sitagliptin vs placebo	No	Twelve-week liraglutide treatment does not reduce hepatic steatosis
2016	Vanderheiden	[89]	71 T2DM patients requiring high-dose insulin treatment	Single-center, randomized, double-blind	Liraglutide vs placebo	Yes	Liraglutide significantly decreased liver fat (evaluated by MR) vs placebo
2016	Armstrong	[56]	52 NASH patients	Multicentre, double-blinded, phase 2 trial	Liraglutide vs placebo	Yes	Liraglutide 1.8 mg/day led to histological resolution of NASH in 39% of patients
2017	Bouchi	[90]	17 insulin-treated T2DM patients	Randomized, open-label	Liraglutide + insulin vs insulin	Yes	Liraglutide reduces visceral adiposity and hepatic fat accumulation
2017	Feng	[77]	87 T2DM and NAFLD patients	RCT	Liraglutide vs gliclazide vs metformin	Yes	Liraglutide causes a greater reduction of intrahepatic fat than gliclazide
2017	Petit	[57]	68 uncontrolled T2DM patients	Prospective single-center	Liraglutide	Yes	Liraglutide 1.2 mg/day significantly reduced liver fat content by body weight reduction
2018	Frøssing	[58]	72 obese/overweight patients with PCOS	Prospective double-blind	Liraglutide vs placebo	Yes	Liraglutide treatment reduced liver fat content by 44% (evaluated by MR spectroscopy) compared with placebo
2019	Yan	[50]	75 NAFLD and metformin-uncontrolled T2DM patients	RCT	Liraglutide vs sitagliptin vs insulin glargine	Yes	Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced intrahepatic lipid and visceral adipose tissue
2021	Colosimo	[81]	637 T2DM patients	Retrospective	DPP-4i vs GLP-1 RA vs SGLT-2i vs others	Yes	GLP-1 RA and SGLT-2Is improve biomarkers of steatosis (FLI)
2021	Newsome	[61]	320 obese/overweight NASH patients	Prospective double-blind	Semaglutide vs placebo	Yes	Semaglutide treatment resulted in a significantly higher percentage of patients with NASH resolution than placebo

DPP-4i: dipeptidyl peptidase-4 inhibitors; FLI: fatty liver index; GLP-1 RA: Glucagon-like peptide-1 receptor agonists; MR: magnetic resonance; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; NS: not specified; PCOS: polycystic ovary syndrome; RCT: Randomized Controlled Trial; SGLT2i: Sodium-glucose Cotransporter-2 inhibitors; T2DM: type 2 diabetes mellitus.