Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non‐alcoholic fatty liver disease

• Published in: Liver international Vol. 39; no. 5; pp. 941 - 949
• Main Authors: Khoo, Joan, Hsiang, John C., Taneja, Ranu, Koo, Seok‐Hwee, Soon, Gaik‐Hong, Kam, Carmen J., Law, Ngai‐Moh, Ang, Tiing‐Leong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-05-2019
• Subjects: Adults; Alanine; Alanine transaminase; Apoptosis; Body mass; Body weight loss; Caspase; Cholecystokinin; Cytokeratin; Fatty liver; GLP‐1 agonist; Glucagon; Lifestyles; Liver; Liver diseases; Magnetic resonance imaging; NAFLD; obesity; Steatosis; Weight loss; Weight reduction; weight loss; NAFLD; GLP-1 agonist; obesity
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.14065

Background & Aims
We compared the effects of weight loss induced with the glucagon‐like peptide‐1 agonist liraglutide, with that of lifestyle modification, followed by weight maintenance after discontinuing intervention, in obese adults with non‐alcoholic fatty liver disease (NAFLD).
Methods
Thirty obese (mean age 40.7 ± 9.1 years, BMI 33.2 ± 3.6 kg/m2, 90% male) adults with NAFLD defined as liver fat fraction (LFF) > 5% on magnetic resonance imaging without other causes of hepatic steatosis were randomized to a supervised programme of energy restriction plus moderate‐intensity exercise to induce ≥ 5% weight loss (DE group, n = 15), or liraglutide 3 mg daily (LI group, n = 15) for 26 weeks, followed by 26 weeks with only advice to prevent weight regain.
Results
Diet and exercise and LI groups had significant (P < 0.01) and similar reductions in weight (−3.5 ± 3.3 vs −3.0 ± 2.2 kg), LFF (−8.1 ± 13.2 vs −7.0 ± 7.1%), serum alanine aminotransferase (−39 ± 35 vs −26 ± 33 U/L) and caspase‐cleaved cytokeratin‐18 (cCK‐18) (−206 ± 252 vs −130 ± 158 U/L) at 26 weeks. At 52 weeks, the LI group significantly (P < 0.05) regained weight (1.8 ± 2.1 kg), LFF (4.0 ± 5.3%) and cCK‐18 (72 ± 126 U/L), whereas these were unchanged in the DE group.
Conclusions
Liraglutide was effective for decreasing weight, hepatic steatosis and hepatocellular apoptosis in obese adults with NAFLD, but benefits were not sustained after discontinuation, in contrast with lifestyle modification. Continuing the exercise learned in the structured programme contributed to the maintenance of liver fat reduction.