Background: Nonalcoholic fatty liver disease (NAFLD) in adolescents is rising alongside obesity, and effective, scalable treatments are needed. Lifestyle intervention is first-line, while glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise for weight and metabolic control. We conducted a pilot randomized controlled trial to compare hepatic and metabolic effects of intensive, family-supported lifestyle intervention versus GLP-1RA therapy in overweight adolescents with NAFLD.
Methods: In this multicenter, parallel-group pilot RCT, adolescents aged 12-17 years with BMI ≥85th percentile and MRI-proton density fat fraction (MRI-PDFF) ≥8% were randomized 1: 1 to (A) intensive lifestyle (nutrition, activity, behavioral support) or (B) GLP-1RA plus brief lifestyle advice. The primary endpoint was change in MRI-PDFF at Week 24. Key secondary endpoints included ALT, BMI z-score, HOMA-IR, waist circumference, feasibility metrics (retention, imaging completion, adherence), and safety. Analyses followed intention-to-treat with between-arm comparisons using ANCOVA/t-tests.
Results: Sixty participants were randomized (n=30/arm). At Week 24, mean MRI-PDFF decreased in both arms, favoring GLP-1RA: −3. 58±3. 04% (lifestyle) vs −5. 52±3. 02% (GLP-1RA); p=0. 016. ALT fell by −9. 92±17. 28 U/L vs −20. 05±16. 61 U/L; p=0. 024. BMI z-score declined −0. 15±0. 22 vs −0. 38±0. 16; p<0. 001. HOMA-IR improved −0. 31±1. 21 vs −1. 33±1. 40; p=0. 004, and waist circumference decreased −3. 47±4. 16 cm vs −6. 65±4. 11 cm; p=0. 004 (lifestyle vs GLP-1RA, respectively). Feasibility targets were achieved for retention and MRI-PDFF completion in both arms; lifestyle session attendance and medication persistence were acceptable for a pilot. Gastrointestinal adverse events were more frequent with GLP-1RA (13. 3% vs 30. 0%); serious adverse events were uncommon and balanced.
Conclusions: In overweight adolescents with NAFLD, GLP-1RA therapy produced greater short-term reductions in hepatic fat and metabolic risk markers than an intensive lifestyle program, with expected gastrointestinal tolerability. Both strategies improved outcomes versus baseline, supporting a stepwise care model in which structured lifestyle is foundational and GLP-1RA may serve as an adjunct for youths with persistent steatosis or elevated cardiometabolic risk. Findings justify a larger, longer trial powered for histologic/fibrosis-sensitive endpoints and patient-centered outcomes.
International Journal of Paediatrics and Geriatrics
