Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Table 2 Characteristics and outcomes of clinical studies that evaluated the effects of liraglutide and semaglutide on non-alcoholic fatty liver disease

Ref.	Type of study; country	Number of patients	Treatment	Effects on NAFLD
Kahal et al[45], 2014	Prospective; United Kingdom	36	Liraglutide 0.9 mg/d for 6 mo	Serum procollagen type 3 amino-terminal peptide levels, a marker of hepatic fibrosis, decreased in women with PCOS
Eguchi et al[46], 2014	Prospective; Japan	26	Liraglutide 0.9 mg/d for 24-96 wk	ALT activity decreased. NASH decreased in 6/10 patients who underwent repeat biopsy at 96 wk
Suzuki et al[47], 2013	Retrospective; Japan	46	Liraglutide 0.9 mg/d for 6 mo	Liver to kidney attenuation ratio in CT (an index of hepatic steatosis) increased
Ohki et al[48], 2012	Retrospective; Japan	82	Liraglutide 0.9 mg/d for 340 d or sitagliptin 50-100 mg/d for 250 d or pioglitazone 15 mg/d for 1200 d	ALT activity was reduced with all agents. Liraglutide and pioglitazone but not sitagliptin reduced the APRI score
Jendle et al[49], 2009	Randomized controlled; multicenter	160	Liraglutide 0.6, 1.2 or 1.8 mg/d or glimepiride 4 mg/d or placebo for 26 wk	Liver to spleen attenuation ratio in CT (a marker of hepatic steatosis) increased in patients treated with liraglutide 1.8 mg/d and did not change in those treated with lower doses of liraglutide or glimepiride. ALT activity showed comparable decreases with both agents
Khoo et al[50], 2009	Randomized controlled; Singapore	30	Liraglutide 3 mg/d for 16 wk or lifestyle modification	Liraglutide was effective for decreasing weight, hepatic steatosis and hepatocellular apoptosis, but benefits were not sustained after discontinuation, in contrast with lifestyle modification
Feng et al[51], 2017	Randomized controlled; China	87	Liraglutide, metformin, or gliclazide for 24 wk	Liraglutide has better results in improving liver function, reductions in intrahepatic fat content and HbA1c level, and weight loss than metformin and gliclazide
Bouchi et al[52], 2017	Randomized controlled; Japan	19	Liraglutide 0.9 mg/d plus insulin or insulin alone for 14 wk	Liraglutide reduces visceral fat, hepatic fat accumulation, albuminuria and micro-inflammation and improves QOL
Petit et al[53], 2017	Prospective; France	68	Liraglutide 1.2 mg/d for 6 mo	Liraglutide significantly reduced liver fat content
Armstrong et al[54], 2016	Double-blind, randomized, controlled; multicenter United Kingdom	52	Liraglutide 1.8 mg/d or placebo for 48 wk	Liraglutide led to histological resolution of NASH
Smits et al[55], 2016	Randomized placebo-controlled; Holland	52	Liraglutide 1.8 mg/d, sitagliptin 100 mg/d or placebo	Liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis
Zhang et al[56], 2016	Randomized controlled; China	835	Liraglutide 1.2 mg/d or metformin 500 mg/3 times per day	Liraglutide improves the blood glucose and lipid levels as well as liver function
Tian et al[57], 2018	Randomized controlled; China	127	Liraglutide 0.6-1.2 mg/d or metformin 1000-1500 mg/d for 12 wk	Liraglutide decreases ALT levels and is more effective than metformin at alleviating liver inflammation and improving liver function
Cuthbertson et al[33], 2012	Prospective; United Kingdom	25	Exenatide 10 mg twice daily or liraglutide 1.2 mg/d	Both liraglutide and exenatide reduce body weight, HbA1c and intrahepatic lipid accumulation
Newsome et al[58], 2019	Retrospective (data from 2 trials); United Kingdom	957 (trial 1) and 3297 (trial 2)	Semaglutide 0.05, 0.1, 0.2, 0.3 or 0.4 mg/d for 52 wk (trial 1) and semaglutide 0.5 or 1.0 mg/wk for 104 wk (trial 2)	Semaglutide significantly reduced ALT and hsCRP in clinical trials in subjects with obesity and/or type 2 diabetes

PCOS: Polycystic ovary syndrome; NAFLD: Non-alcoholic fatty liver disease; ALT: Alanine transaminase; hsCRP: High-sensitivity C-reactive protein; NASH: Non-alcoholic steatohepatitis; CT: Computed tomography; APRI: AST to platelet count ratio index.