Enhancing Weight Loss Maintenance With GLP-1RA (BYDUREON™) in Adolescents With Severe Obesity

Summary

Long-term weight loss maintenance is seldom achieved by individuals with obesity owing to numerous biological adaptations involving appetite, satiety, and energy expenditure in the post- weight loss setting. Following a loss in body weight, peripheral and central mechanisms convey a sense that energy reserves have dwindled, activating a strong counter response to increase caloric intake. Adolescents with severe obesity are not immune to the vexing issue of weight regain. Indeed, only 2% are able to achieve and maintain clinically-meaningful weight loss with lifestyle modification therapy. Therefore, novel treatment paradigms focused on long-term weight loss maintenance are urgently needed. Pharmacotherapy has the potential to prevent weight regain by targeting specific counter-regulatory mechanisms in the post- weight loss setting. One of the most promising candidates is the glucagon like peptide-1 receptor agonist (GLP-1RA) class, which greatly enhanced weight loss maintenance following a short-term low calorie diet among adults with obesity. The rationale for focusing on GLP-1RA treatment (BYDUREON™) to prevent weight regain is supported by the multiple central and peripheral mechanisms of action targeted by this class of drug; many of which specifically address the biological adaptations known to induce relapse. The investigators have strong preliminary data demonstrating that GLP-1RA treatment reduces BMI in adolescents with severe obesity. Moreover, the investigators and others have shown that although meal replacement therapy (structured meals of known caloric content) can elicit robust short-term weight loss among adolescents with severe obesity, weight regain is a pervasive problem. Therefore, in this clinical trial, our innovative approach will utilize GLP-1RA treatment to target weight regain following short-term meal replacement therapy in youth with severe obesity. Participants who achieve ≥5% BMI reduction during the meal replacement phase will be randomized to GLP-1RA treatment or placebo for an additional 52 weeks while simultaneously engaging in lifestyle modification therapy. Importantly, this study will also allow us to examine the extent to which GLP-1RA treatment addresses mechanisms of weight regain, investigate other pleiotropic benefits of GLP-1RA, and identify predictors of weight loss response.

Timeline

Start

2015-12

Primary completion

2020-08-14

Completion

2020-08-14

Publications

• Rode JB, Wolf JM, Bolan PJ, Palzer E, Rudser KD, Aboobacker S, Fox CK, Kelly AS, Ryder JR. Meal Replacement Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents with Severe Obesity. Child Obes. 2026 Jun 11:21532176261457202. doi: 10.1177/21532176261457202. Online ahead of print.
• Saunders SL, Clark JM, Rudser K, Chauhan A, Ryder JR, Bolan PJ. Comparison of automatic liver volumetry performance using different types of magnetic resonance images. Magn Reson Imaging. 2022 Sep;91:16-23. doi: 10.1016/j.mri.2022.05.002. Epub 2022 May 7.
• Fox CK, Clark JM, Rudser KD, Ryder JR, Gross AC, Nathan BM, Sunni M, Dengel DR, Billington CJ, Bensignor MO, Kelly AS. Exenatide for weight-loss maintenance in adolescents with severe obesity: A randomized, placebo-controlled trial. Obesity (Silver Spring). 2022 May;30(5):1105-1115. doi: 10.1002/oby.23395. Epub 2022 Apr 10.
• Ryder JR, Kaizer AM, Rudser KD, Daniels SR, Kelly AS. Utility of Body Mass Index in Identifying Excess Adiposity in Youth Across the Obesity Spectrum. J Pediatr. 2016 Oct;177:255-261.e2. doi: 10.1016/j.jpeds.2016.06.059. Epub 2016 Aug 2.

Drugs

Indications