Meal Replacement Therapy for Metabolic Dysfunction–Associated Steatotic Liver Disease in Adolescents with Severe Obesity

Abstract

Background:

This clinical trial evaluated hepatic fat content and weight loss in adolescents with severe obesity and metabolic dysfunction–associated steatotic liver disease (MASLD) following short-term meal replacement therapy (MRT).

Methods:

Adolescents aged 12–17 years with severe obesity (BMI ≥1.2 × 95th percentile or ≥35 kg/m²) and magnetic resonance imaging–confirmed MASLD (hepatic fat fraction [HFF] ≥5%) completed a 4- to 8-week MRT program (∼500 kcal/day deficit) targeting ≥5% BMI reduction. Participants underwent ¹H-magnetic resonance spectroscopy at baseline and at follow-up, along with 2-hour mixed-meal tolerance testing.

Results:

Seventeen adolescents [baseline mean (standard deviation or SD) BMI = 39.9 (4.1) kg/m²; age = 16.0 (1.6) years; 65% male; HFF = 15.6 (5.1)%] demonstrated a mean absolute decrease in BMI of 5.6% [−2.23 kg/m²; 95% confidence interval (CI): −2.45, −2.02; p < 0.001] and a 37.3% relative reduction (95% CI: 26.4%, 48.1%; p < 0.001) in HFF. Despite HFF reduction, 13 out of 17 had MASLD at study conclusion. Decrease in HFF corresponded to significant reductions in triglycerides [difference (95% CI): −5.8 mg/dL (−9.4, −2.1); p = 0.012], glucose area under the curve (AUC) [−2.2 mg/dL (−3.2, −1.3); p = 0.021], and leptin AUC [−40.5 pg/mL (−57.1, −23.9); p = 0.009]. No significant difference in alanine aminotransferase was observed.

Conclusions:

Short-term MRT was associated with reductions in liver fat and improvements in metabolic biomarkers among adolescents with MASLD. Large-scale trials are needed to evaluate the implementation of MRT as part of a multimodal treatment strategy in this population. [Clinical Trial Registration: Enhancing Weight Loss Maintenance with GLP-1 RA (BYDUREON™) in Adolescents With Severe Obesity, NCT02496611, https://clinicaltrials.gov/study/NCT02496611].