Liraglutide (Saxenda(R)) in Adolescents With Obesity After Sleeve Gastrectomy

Study Description: This trial is an open-label Phase II non-randomized pilot study conducted at the NIH Clinical Center to investigate the efficacy of daily subcutaneous injection of liraglutide, a glucagon-like peptide-1 (GLP1) analogue to promote reduction of body mass index (BMI) in adolescents who continue to have obesity (BMI (Bullet)30 or BMI \>=95th percentile for age and sex) 1 year or more after vertical sleeve gastrectomy (SG). We hypothesize that administration of liraglutide will be associated with reduction in BMI in such adolescents. Objectives: Primary objective: To determine the effect size for the change in BMI of liraglutide 3.0 mg daily subcutaneously at 16 weeks in adolescents who have obesity after SG, in order to use the observed changes to determine the sample size of a subsequent randomized, controlled investigation. Hypothesis: The Primary Endpoint is estimation of required sample size for a later randomized controlled trial through calculation of effect size for change in body mass index (BMI) from baseline to 16 weeks of liraglutide. The hypothesis is: The data will be sufficient to calculate the effect size for change in BMI from baseline to 16 weeks for a 2-group experiment (placebo versus liraglutide). Secondary objectives: To study the effects of 16 weeks of liraglutide 3.0 mg subcutaneously on change in mean BMI and fat mass in adolescents who underwent vertical sleeve gastrectomy (SG) \>=1y prior to study initiation but still have obesity or have a recrudescence of obesity despite surgery. To compare the effects of liraglutide on BMI and fat mass in enrolled participants who had a poor initial response to SG (\<20% BMI reduction at BMI nadir) vs. those with a typical post-SG weight loss (\>=20% BMI reduction at BMI nadir). Additional Objectives: To examine the effects of daily subcutaneous liraglutide in enrolled participants on changes in body composition, metabolic syndrome markers, energy intake, glucose tolerance, gastrointestinal (GI) hormone concentrations, appetite, free living physical activity, mood, suicidality, weight related quality of life, self-perception of body image, and secretome. Endpoints: Primary Endpoint: Estimation of required sample size for a later RCT through calculation of effect size for change in body mass index (BMI) from baseline to 16 weeks of liraglutide. Key Secondary Endpoints: Changes in BMI and fat mass after 16 weeks of liraglutide Comparison of changes in BMI and fat mass after 16 weeks of liraglutide in participants who had a poor initial response to SG (\<20% BMI reduction at BMI nadir) vs. those with a typical post-S weight loss (\>=20% BMI reduction at BMI nadir) Tolerability and safety of liraglutide 3.0 mg. Additional (exploratory) Endpoints: Change from baseline to 16 weeks of liraglutide in: 1. Proportion reducing BMI by at least 5% and 10% 2. BMI standard deviation score for age and sex (BMIz) 3. Body weight 4. Percentage total body fat mass by DXA 5. Appetite score using visual analog scale (VAS) 6. Attention bias to highly palatable images 7. Energy intake at buffet meal 8. Free living physical activity by accelerometry 9. Metabolic syndrome markers (waist circumference, systolic and diastolic blood pressure, lipids, fasting plasma glucose level) 10. Fasting plasma insulin and HOMA-IR index 11. 2-hour oral glucose tolerance test (OGTT) insulin and glucose measurements 12. Hemoglobin A1C 13. Plasma GI hormones (GLP-1 and PYY) during OGTT 14. Weight related quality of life (QoL) score 15. Beck Depression Inventory total score 16. Body-Esteem Scale Score for Adolescents and Adults 17. Columbia Suicide Severity Rating Scale 18. Secretome analysis 19. Stool microbiome analysis