Young Adults With Early-onset Obesity Treated With Semaglutide

Summary

Introduction: The increasing prevalence of obesity is particularly pronounced among adolescents. Currently available treatment options consist of structured lifestyle interventions. However, 25 % of adolescents do not respond to lifestyle treatment, why new effective treatment strategies are needed. Therefore, the aim of this study is to investigate the effect of lifestyle interventions combined with the GLP-1 receptor agonist semaglutide to young adults with otherwise treatment resistant obesity. Methods and analysis: This is an investigator-initiated, randomized, placebo-controlled trial. 180-270 young adults (age 18-28) will be recruited from The Childrens Obesity Clinic (TCOC), Department of Pediatrics, Holbæk Hospital. Based on their previous response to the TCOC protocol the participants will be divided in four groups: Group A: Non-responders: 55-85 young adults with obesity (BMI≥30 kg/m2) who have not reduced adiposity, defined as BMI SDS reduction \<0.1, during the structured lifestyle counselling as children. Group B: Insufficient responders: 55-85 young adults who have reduced adiposity, defined as BMI SDS reduction \>0.25, during the structured lifestyle counselling as children but still have obesity as young adults (BMI≥30 kg/m2) Group C: Excellent responders: 35-50 young adults, who have reduced adiposity, defined as BMI SDS reduction \>0.5, during the structured lifestyle counselling as children and no longer have obesity as young adults (BMI\<30 kg/m2) Group D: Population-based reference group (normal weight development): 35-50 young adults, who have participated in The Holbaek Study as children. Group A and B are randomized 2:1 to either semaglutide or placebo for 68 weeks. Group C and D will attend baseline examinations only and not undergo intervention. The primary endpoint is change in BMI from randomization to end-of-treatment. Ethics and dissemination: The trial has been approved by the Danish Medicines Agency (EudraCT 2019-002274-31) and by the ethical committee of the Capital Region of Denmark (H-20039422). The trial will be conducted in agreement with the Declaration of Helsinki and monitored to follow the guidelines for good clinical practice. Results will be submitted for publication in international peer-reviewed scientific journals.

Timeline

Start

2022-05-30

Primary completion

2026-04-01

Completion

2026-04-01

Publications

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• Background Mollerup PM, Gamborg M, Trier C, Bojsoe C, Nielsen TR, Baker JL, Holm JC. A hospital-based child and adolescent overweight and obesity treatment protocol transferred into a community healthcare setting. PLoS One. 2017 Mar 6;12(3):e0173033. doi: 10.1371/journal.pone.0173033. eCollection 2017.
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• Background Hvidt KN, Olsen MH, Ibsen H, Holm JC. Effect of changes in BMI and waist circumference on ambulatory blood pressure in obese children and adolescents. J Hypertens. 2014 Jul;32(7):1470-7; discussion 1477. doi: 10.1097/HJH.0000000000000188.
• Background Fonvig CE, Chabanova E, Ohrt JD, Nielsen LA, Pedersen O, Hansen T, Thomsen HS, Holm JC. Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle. BMC Pediatr. 2015 Dec 30;15:196. doi: 10.1186/s12887-015-0513-6.
• Background Torekov SS, Holst JJ, Ehlers MR. Dose response of continuous subcutaneous infusion of recombinant glucagon-like peptide-1 in combination with metformin and sulphonylurea over 12 weeks in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2014 May;16(5):451-6. doi: 10.1111/dom.12240. Epub 2013 Dec 10.
• Background Torekov SS, Kipnes MS, Harley RE, Holst JJ, Ehlers MR. Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes. Diabetes Obes Metab. 2011 Jul;13(7):639-43. doi: 10.1111/j.1463-1326.2011.01388.x.
• Background Torekov SS, Madsbad S, Holst JJ. Obesity - an indication for GLP-1 treatment? Obesity pathophysiology and GLP-1 treatment potential. Obes Rev. 2011 Aug;12(8):593-601. doi: 10.1111/j.1467-789X.2011.00860.x. Epub 2011 Mar 15.
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• Background Faerch K, Torekov SS, Vistisen D, Johansen NB, Witte DR, Jonsson A, Pedersen O, Hansen T, Lauritzen T, Sandbaek A, Holst JJ, Jorgensen ME. GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study. Diabetes. 2015 Jul;64(7):2513-25. doi: 10.2337/db14-1751. Epub 2015 Feb 12.
• Background Iepsen EW, Lundgren J, Holst JJ, Madsbad S, Torekov SS. Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36. Eur J Endocrinol. 2016 Jun;174(6):775-84. doi: 10.1530/EJE-15-1116. Epub 2016 Mar 14.
• Background Iepsen EW, Lundgren J, Dirksen C, Jensen JE, Pedersen O, Hansen T, Madsbad S, Holst JJ, Torekov SS. Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss. Int J Obes (Lond). 2015 May;39(5):834-41. doi: 10.1038/ijo.2014.177. Epub 2014 Oct 7.
• Background Lundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, Svane MS, Bandholm T, Bojsen-Moller KN, Blond MB, Jensen JB, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021 May 6;384(18):1719-1730. doi: 10.1056/NEJMoa2028198.
• Background Christensen BJ, Iepsen EW, Lundgren J, Holm L, Madsbad S, Holst JJ, Torekov SS. Instrumentalization of Eating Improves Weight Loss Maintenance in Obesity. Obes Facts. 2017;10(6):633-647. doi: 10.1159/000481138. Epub 2017 Dec 6.
• Background Jensen SBK, Janus C, Lundgren JR, Juhl CR, Sandsdal RM, Olsen LM, Andresen A, Borg SA, Jacobsen IC, Finlayson G, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment. Nat Commun. 2022 Aug 15;13(1):4770. doi: 10.1038/s41467-022-32307-y.
• Background Trier C, Hollensted M, Schnurr TM, Lund MAV, Nielsen TRH, Rui G, Andersson EA, Svendstrup M, Bille DS, Gjesing AP, Fonvig CE, Frithioff-Bojsoe C, Balslev-Harder M, Quan S, Gamborg M, Pedersen O, Angquist L, Holm JC, Hansen T. Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations. Int J Obes (Lond). 2021 Jan;45(1):66-76. doi: 10.1038/s41366-020-00673-6. Epub 2020 Sep 13.
• Background Bonnefond A, Keller R, Meyre D, Stutzmann F, Thuillier D, Stefanov DG, Froguel P, Horber FF, Kral JG. Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study. Diabetes Care. 2016 Aug;39(8):1384-92. doi: 10.2337/dc16-0115. Epub 2016 May 23.
• Background Iepsen EW, Zhang J, Thomsen HS, Hansen EL, Hollensted M, Madsbad S, Hansen T, Holst JJ, Holm JC, Torekov SS. Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist. Cell Metab. 2018 Jul 3;28(1):23-32.e3. doi: 10.1016/j.cmet.2018.05.008. Epub 2018 May 31.
• Background Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sorrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619.

Drugs

Indications

No indication recorded.