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

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/m(2), 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.