Meal Replacement Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents with Severe Obesity.
Short-term meal replacement therapy in adolescents with severe obesity showed a significant reduction in BMI and liver fat, but most participants still had metabolic dysfunction at the end of the study.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
This clinical trial evaluated hepatic fat content and weight loss in adolescents aged 12-17 years with severe obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) following a short-term meal replacement therapy (MRT). The study reported a mean absolute decrease in BMI of 5.6% and a 37.3% relative reduction in hepatic fat fraction (HFF). Despite these reductions, 13 out of 17 participants still had MASLD at the conclusion of the study.
Abstract
<h4>Background</h4>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).<h4>Methods</h4>Adolescents aged 12-17 years with severe obesity (BMI ≥1.2 × 95th percentile or ≥35 kg/m<sup>2</sup>) 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 <sup>1</sup>H-magnetic resonance spectroscopy at baseline and at follow-up, along with 2-hour mixed-meal tolerance testing.<h4>Results</h4>Seventeen adolescents [baseline mean (standard deviation or SD) BMI = 39.9 (4.1) kg/m<sup>2</sup>; 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/m<sup>2</sup>; 95% confidence interval (CI): -2.45, -2.02; <i>p</i> < 0.001] and a 37.3% relative reduction (95% CI: 26.4%, 48.1%; <i>p</i> < 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); <i>p</i> = 0.012], glucose area under the curve (AUC) [-2.2 mg/dL (-3.2, -1.3); <i>p</i> = 0.021], and leptin AUC [-40.5 pg/mL (-57.1, -23.9); <i>p</i> = 0.009]. No significant difference in alanine aminotransferase was observed.<h4>Conclusions</h4>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].
Background
This study addresses the impact of meal replacement therapy (MRT) on adolescents with severe obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Prior research has indicated that obesity and associated liver conditions are prevalent in this demographic, yet effective interventions remain limited. This trial is significant as it explores a potential therapeutic approach to reduce hepatic fat and improve metabolic health in adolescents.
Methods
The study involved a clinical trial design with 17 adolescents aged 12-17 years who had severe obesity (BMI ≥1.2 × 95th percentile or ≥35 kg/m²) and magnetic resonance imaging-confirmed MASLD (HFF ≥5%). Participants underwent a 4- to 8-week MRT program with a caloric deficit of approximately 500 kcal/day, targeting a ≥5% reduction in BMI. Primary outcomes included changes in BMI and HFF, assessed through 1H-magnetic resonance spectroscopy and mixed-meal tolerance testing.
Results
The primary endpoint showed a mean absolute decrease in BMI of 5.6% [-2.23 kg/m²; 95% CI: -2.45, -2.02; p < 0.001]. Additionally, there was a 37.3% relative reduction in HFF (95% CI: 26.4%, 48.1%; p < 0.001). The study also reported significant reductions in triglycerides, glucose AUC, and leptin AUC, with p-values of 0.012, 0.021, and 0.009, respectively. However, no significant difference in alanine aminotransferase was observed.
Interpretation
The findings indicate a statistically significant reduction in BMI and hepatic fat, aligning with previous literature that suggests dietary interventions can positively affect metabolic parameters. However, the clinical significance is limited as 76.5% of participants still had MASLD post-intervention. The small sample size and short follow-up period raise concerns about the generalizability and durability of these results, suggesting that further research is needed to confirm these findings in larger, more diverse populations.
Key findings
- Mean absolute decrease in BMI of 5.6% [-2.23 kg/m²; 95% CI: -2.45, -2.02; p < 0.001]
- 37.3% relative reduction in HFF (95% CI: 26.4%, 48.1%; p < 0.001)
- Triglycerides reduction of -5.8 mg/dL (-9.4, -2.1; p = 0.012)
- Glucose AUC reduction of -2.2 mg/dL (-3.2, -1.3; p = 0.021)
- Leptin AUC reduction of -40.5 pg/mL (-57.1, -23.9; p = 0.009)
- No significant difference in alanine aminotransferase observed.
Limitations
- Small sample size (n=17)
- Short follow-up duration (4 to 8 weeks)
- 13 out of 17 participants still had MASLD at study conclusion
- Single-site study limits generalizability
- No long-term outcomes reported