Lifestyle interventions yield more lasting benefits for NAFLD patients than liraglutide
While liraglutide successfully induces weight loss in obese adults with nonalcoholic fatty liver disease (NAFLD), its benefits were not preserved after discontinuation, unlike that of lifestyle modification, according to a new Singapore study.
“Our findings support the use of liraglutide for the treatment of NAFLD in overweight and obese adults, which should be combined with diet and exercise, and continued even after weight loss has been achieved,” said researchers.
Thirty obese adults with NAFLD (mean age 40.7±9.1 years; 90 percent male) were randomly assigned to receive a supervised programme of energy restriction with moderate-intensity exercise (n=15) or 3-mg liraglutide (n=16). Participants who received liraglutide experienced gastrointestinal symptoms such as nausea and bloating, but none reported vomiting or pancreatitis. [Liver Int 2019;doi:10.1111/liv.14065]
During the first 26 weeks, both the lifestyle modification (change, –1.3±1.2 kg/m2; p=0.003) and liraglutide (change, –1.0±0.7 kg/m2; p<0.001) interventions resulted in a significant drop in body mass index (BMI).
Similar significant effects were observed for other anthropometric measures, such as weight (lifestyle: change, –3.5±3.3 kg; p=0.006; liraglutide: change, –3.0±2.2 kg; p=0.001), waist circumference (lifestyle: change, –4.4±3.6 cm; p=0.001; liraglutide: change, –5.6±4.1 cm; p<0.001) and total fat mass (lifestyle: change, –2.3±2.8 kg; p=0.01; liraglutide: change, –2.1±1.7 kg; p<0.001).
Notably, during the same time span, there were also significant reductions in liver fat fraction (LFF; p=0.03, p=0.003), liver stiffness (p=0.04, p=0.007) and caspase-cleaved CK18 (cCK18), a marker of hepatocyte apoptosis (p=0.01, p=0.009), in the lifestyle and liraglutide groups.
Weight loss in the lifestyle group remained stable over the next 26 weeks after interventions were terminated. Change in BMI (p=0.99), weight (p=0.99) and total fat mass (p=0.76) between weeks 26 and 52 failed to reach statistical significance. The same was true for change in liver stiffness (p=0.34), LFF (p=0.31) and cCK18 (p=0.33).
In contrast, participants in the liraglutide group showed significant rebound. From the week-26 values, there were significant increases in BMI (change, 0.6±0.7 kg/m2; p=0.02) and weight (change, 1.8±2.1 kg; p=0.02), as well as in LFF (change, 4.0±5.3 percent; p=0.01) and cCK18 (change 72±126 U/L; p=0.05).
Moreover, according to researchers, “[d]uring the weight maintenance phase, liver fat continued to decrease in the [lifestyle intervention] group despite unchanged systemic insulin resistance, and the amount of exercise during the weight maintenance phase was inversely associated with changes in weight, WC, total fat mass, liver fat and cCK18.”
Along with findings from prior studies, this further highlights the protective effects of physical activity against NAFLD and its value in preventing the accumulation of hepatic fat, they added. [Liver Int 2017;37:919-926]
“Larger studies of longer duration, comparing varying durations of combined [glucagon-like peptide-1] agonist and lifestyle modification, and evaluating persistence of effects on weight and NAFLD, would shed further insights on the long-term use of liraglutide for NAFLD,” researchers said.