Diabetes and fatty liver: Involvement of incretin and its benefit for fatty liver management

Table 1 Randomized-controlled trials of glucagon-like peptide-1 receptor agonists related to fatty liver diseases

Ref.	Subjects	Intervention (dose)	Comparator	Effects
Jendle et al[59], 2009	T2DM	Liraglutide (1.8-1.2-0.6 mg/day) with additional metformin administration	Glimepiride 4 mg or placebo with metformin	10% attenuation ratio of liver-spleen
Fan et al[60], 2013	Overweight T2DM	Exenatide (2 x 10µg)	Metformin	Decrease in liver enzyme
Shao et al[61], 2014	Overweight/obese T2DM	Exenatide (2 x 10 µg)	Insulin glargine	Decrease of liver enzymes and degree of fatty liver on ultrasound
Tang et al[62], 2015	Overweight/obese T2DM	Liraglutide 0.6 to 1.8 mg/day	Insulin glargine	No difference in the decrease of liver fat
Armstrong et al[63], 2016	Overweight/obese (17 out of 52 subjects with T2DM)	Liraglutide (1.8 mg/day)	Placebo	Improvement in NASH histology by 39%
Smits et al[64], 2016	Overweight/obese T2DM	Liraglutide (1.8 mg/day)	Sitagliptin, placebo	No difference in liver fat content
Dutour et al[65], 2016	T2DM	Exenatide 5-10 mcg twice a day	Placebo	Significant decrease in body weight and liver fat content in the exenatide group
Khoo et al[66], 2017	Obesity patients without T2DM	Liraglutide (3 mg/day)	Lifestyle intervention	No difference in reducing liver fat
Feng et al[67], 2017	T2DM	Liraglutide (1.8 mg/day)	Metformin or glicazide	Improvement in hepatic/renal index ratio
Frøssing et al[68], 2018	Women with PCOS and NAFLD	Liraglutide 1.8 mg/day	Placebo	Decrease of body weight by 5.2 kg (5.6% from baseline), liver fat content by 44%, decrease the prevalence of NAFLD by about two-thirds and decrease of fasting blood glucose
Yan et al[69], 2019	T2DM and NAFLD	Liraglutide 1.8 mg/day	Insulin glargine and sitagliptin	Decreased liver fat content, reduction of HbA1c levels in all groups, decrease in body weight
Khoo et al[70], 2019	Obese and NAFLD	Liraglutide 3.0 mg/day	Lifestyle changing	The two groups had decrease of liver fat content
Liu et al[71], 2020	T2DM and NAFLD	Exenatide 1.8 mg/day	Insulin glargine	Decrease of liver fat content, greater reduction of visceral adipose tissue
Bizino et al[72], 2020	T2DM and NAFLD	Liraglutide 1.8 mg/day	Placebo	Reduced body weight, but the liver content was not different
Kuchay et al[73], 2020	T2DM and NAFLD	Dulaglutide 1.5 mg/week	Placebo	Control-corrected absolute change in liver fat content of -3.5% and relative change of -26.4%
Newsome et al[74], 2020	NASH and liver fibrosis	Semaglutide 0.1 mg/day, 0.2 mg/day, and 0.4 mg/day	Placebo	A higher percentage of NASH resolution without worsening of fibrosis, dose-dependent decrease of serum ALT and AST, and higher mean percentage weight loss

ALT: Alanine transaminase; AST: Aspartate transaminase; HbA1c: Hemoglobin A1c; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; PCOS: Polycystic ovary syndrome; T2DM: Type 2 diabetes mellitus.