Comparative effects of liraglutide 3 mg vs structured lifestyle modification on body weight, liver fat and liver function in obese patients with non‐alcoholic fatty liver disease: A pilot randomized trial

Abstract

We compared the effects of weight loss induced by the glucagon-like peptide 1-agonist liraglutide with a structured lifestyle intervention in obese adults with non-alcoholic fatty liver disease (NAFLD). Obese (body mass index ≥30 kg/m , mean weight 96.0 ± 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on magnetic resonance imaging without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/d) plus moderate-intensity aerobic exercise (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had significant (P < .01) and similar reductions in weight (-3.5 ± 3.3 vs -3.5 ± 2.1 kg, respectively, P = .72), LFF (-8.9 ± 13.4 vs -7.2% ± 7.1%, P = .70), serum alanine aminotransferase (-42 ± 46 vs -34 ± 27 U/L, P = .52) and aspartate aminotransferase (-23 ± 24 vs -18 ± 15 U/L, P = .53). In this first randomized study comparing the 2 weight-loss modalities for improving NAFLD, liraglutide was as effective as structured lifestyle modification.

Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of non-alcoholic steatohepatitis

“…Our present study revealed that once-daily injection of liraglutide for 2 weeks decreased caloric intake and body weight, improved glucose tolerance, and protected from HFCC-CDX-induced insulin resistance, which are well-known effects of liraglutide in humans [27,28]. In addition, we observed that liraglutide could resolve hypertriglyceridemia and reduce hepatic steatosis, oxidative stress, and systemic and hepatic inflammation but not fibrosis, results that are in general agreement with the effects of liraglutide documented in preclinical studies with mice [29][30][31] and clinical trials for NASH [32][33][34]. In NAFLD patients, plasma ALT and AST levels have been found to decrease gradually during liraglutide treatment [32][33][34].…”

“…In addition, we observed that liraglutide could resolve hypertriglyceridemia and reduce hepatic steatosis, oxidative stress, and systemic and hepatic inflammation but not fibrosis, results that are in general agreement with the effects of liraglutide documented in preclinical studies with mice [29][30][31] and clinical trials for NASH [32][33][34]. In NAFLD patients, plasma ALT and AST levels have been found to decrease gradually during liraglutide treatment [32][33][34]. In our experimental setting, liraglutide could indeed significantly decrease the total NAFLD activity score but could not counter the HFCC-CDX-induced increase in plasma ALT and AST, in agreement with results from another dietary mouse model of NASH [30].…”

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

“…In the Lira‐NAFLD study in obese diabetic adults, liver fat content decreased in association with liraglutide‐induced weight loss. Our pilot comparison study of liraglutide to lifestyle modification found that 26 weeks of daily liraglutide induced similar weight loss of ~4% and reductions in hepatic steatosis compared to a supervised structured programme of diet and exercise.…”

Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review

“…Multiple publications have reported beneficial effects to reduce liver fat content and improve ALT, and one study has suggested a benefit in reducing progression of fibrosis (5,10,34,50). Twenty publications reported the effects of a GLP-1 analog on liverrelated endpoints; 12 of these investigated liraglutide (5,6,11,19,20,22,34,44,50,60,65,66), and 8 investigated exenatide (10,13,14,17,18,55,56,58). Four of these reported randomized, controlled, double-blind studies of liraglutide with a placebo (n = 3) or active (n = 1) comparator, and only one of these, the "Liraglutide Safety and Efficacy in Patients with Non-alcoholic Steatohepatitis (LEAN)" study, assessed histological endpoints using biopsy.…”