Download PDF
Adipositas - Ursachen, Folgeerkrankungen, Therapie 2023; 17(03): 115-125
DOI: 10.1055/a-2079-9133
Originalarbeit

Effekte einer Therapie mit Liraglutid bei Jugendlichen mit extremer Adipositas unter Real-Life-Bedingungen

Effects of Liraglutide Treatment in Youth with Extreme Obesity in a Real-Life Setting
Melanie Schirmer  ‡
,
Stephanie Brandt  ‡
1   Sektion Pädiatrische Endokrinologie und Diabetologie, Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Ulm, Ulm, Deutschland
,
Stefanie Zorn 
1   Sektion Pädiatrische Endokrinologie und Diabetologie, Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Ulm, Ulm, Deutschland
,
Martin Wabitsch 
1   Sektion Pädiatrische Endokrinologie und Diabetologie, Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Ulm, Ulm, Deutschland
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Zusammenfassung

Bisher zur Verfügung stehende Maßnahmen zur Reduktion und Stabilisierung des Körpergewichts bei Kindern und Jugendlichen mit Adipositas und extremer Adipositas beschränkten sich auf Interventionen durch eine Lebensstilmodifikation, die jedoch häufig nicht in einer langfristigen und klinisch relevanten Gewichtsreduktion resultieren. Metabolisch-chirurgische Operationen werden zunehmend auch im jugendlichen Alter durchgeführt mit der größten Effektivität hinsichtlich einer Reduktion des Körpergewichts, stellen jedoch aufgrund der perioperativen Risiken und der langfristigen Konsequenzen nur im Einzelfall die Therapie der Wahl dar.

Mit dem GLP-1-Agonisten Liraglutid steht nun erstmals in Europa eine medikamentöse Therapie zur Gewichtsreduktion bei Jugendlichen mit Adipositas ab 12 Jahren zur Verfügung. In einer klinischen Studie konnte gezeigt werden, dass die Gabe von Liraglutid 3,0 mg über 52 Wochen, in Kombination mit einer begleitenden Lebensstil-modifizierenden Intervention, bei Jugendlichen zu einer durchschnittlichen BMI-Reduktion von 4,6% führte [1]. Jedoch gibt es bislang kaum Erfahrungsberichte über den Effekt der Liraglutid-Therapie bei Kindern und Jugendlichen>12 Jahren in der Praxis, unter Real-Life Bedingungen. Wir berichten nachfolgend über Erfahrungen aus der Praxis hinsichtlich der Anwendung von Liraglutid (maximale Dosis 3,0 mg) bis zu 9 Monaten bei n=8 Jugendlichen mit extremer Adipositas, die in der Universitätsklinik für Kinder- und Jugendmedizin Ulm behandelt werden, bezogen auf das Körpergewicht, den BMI sowie die Angabe über berichtete Nebenwirkungen.

Abstract

Treatment options to reduce body weight in children and adolescents with obesity and extreme obesity are limited to lifestyle modifications, which, however, often do not result in long-term and clinically relevant body weight reduction. Metabolic surgery is increasingly being performed in adolescence with extreme obesity with the greatest effectiveness in reducing body weight. Due to the perioperative risks and long-term consequences, this treatment is only an option in selected individual cases. With the GLP-1 agonist liraglutide, a drug therapy for weight reduction in adolescents from 12 years of age is now available for the first time in Europe. In a clinical trial, it was shown that the administration of liraglutide 3.0 mg over 52 weeks, in combination with an accompanying lifestyle modification, led to an average BMI reduction of 4.6% in adolescents [1]. There are only few reports on the effect of liraglutide therapy in children and adolescents>12 years of age under real-life conditions. In the following, we report on experience with the use of liraglutide (maximum dose 3.0 mg) in n=8 adolescents with extreme obesity treated at the center for children and adolescents with obesity (Clinic for Pediatrics and Adolescent Medicine, Ulm University Medical Center), in terms of effect of liraglutide therapy on body weight, BMI, BMI-SDS velocity, on hunger and reported side effects.

Schlüsselwörter

Adipositas - Kinder und Jugendliche - Liraglutid - GLP-1

Key words

obesity - children - adolescents - liraglutide - GLP-1


Publication History

Article published online:
04 September 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Kelly AS, Auerbach P, Barrientos-Perez M. et al. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med 2020; 382: 2117-2128 DOI: 10.1007/s12325-021-01710-0.
    CrossrefPubMedGoogle Scholar
  • 2 World Health Organization. Regional Office for Europe. (2022). WHO European Regional Obesity Report. 2022 https://apps.who.int/iris/handle/10665/353747. Lizenz: CC BY-NC-SA 3.0 IGO; 2022
    PubMedGoogle Scholar
  • 3 Hales CM, Carroll MD, Fryar CD. et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020; 1-8
    PubMedGoogle Scholar
  • 4 Schienkiewitz A, Damerow S, Schaffrath Rosario A. et al. Body mass index among children and adolescents: prevalences and distribution considering underweight and extreme obesity: Results of KiGGS Wave 2 and trends. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2019; 62: 1225-1234 DOI: 10.1007/s00103-019-03015-8.
    CrossrefPubMedGoogle Scholar
  • 5 Reinehr T, Hoffmeister U, Mann R. et al. Medical care of overweight children under real-life conditions: the German BZgA observation study. Int J Obes (Lond) 2009; 33: 418-423 DOI: 10.1038/ijo.2009.50.
    CrossrefPubMedGoogle Scholar
  • 6 Wille N, Bullinger M, Holl R. et al. Health-related quality of life in overweight and obese youths: results of a multicenter study. Health Qual Life Outcomes 2010; 8: 36
    CrossrefPubMedGoogle Scholar
  • 7 Arbeitsgemeinschaft Adipositas im Kindes- und Jugendalter (AGA). S3-Leitlinie Therapie und Prävention der Adipositas im Kindes- und Jugendalter. 2019
    PubMed
  • 8 Mühlig Y, Wabitsch M, Moss A. et al. Weight loss in children and adolescents. Dtsch Arztebl Int 2014; 111: 818-824
    CrossrefPubMedGoogle Scholar
  • 9 Danielsson P, Kowalski J, Ekblom Ö. et al. Response of severely obese children and adolescents to behavioral treatment. Arch Pediatr Adolesc Med 2012; 166: 1103-1108 DOI: 10.1001/2013.jamapediatrics.31910.1159/000336060.
    CrossrefPubMedGoogle Scholar
  • 10 Hoffmeister U, Molz E, Bullinger M. et al. Evaluation of obesity treatment in children and adolescents (EvAKuJ Study). Role of therapeutic concept, certification, and quality indicators. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2011; 54: 603-610 DOI: 10.1007/s00103-011-1257-6.
    CrossrefPubMedGoogle Scholar
  • 11 Brandt S, König D, Lennerz B. et al. Case series: BMI long courses in patients with extreme juvenile obesity. Short- and long-term success of long-term inpatient treatment. MMW Fortschr Med 2016; 158: 1-7 DOI: 10.1007/s15006-016-8606-1.
    CrossrefPubMedGoogle Scholar
  • 12 Shoar S, Mahmoudzadeh H, Naderan M. et al. Long-Term Outcome of Bariatric Surgery in Morbidly Obese Adolescents: a Systematic Review and Meta-Analysis of 950 Patients with a Minimum of 3 years Follow-Up. Obes Surg 2017; 27: 3110-3117 DOI: 10.1007/s11695-017-2738-y.
    CrossrefPubMedGoogle Scholar
  • 13 Arbeitsgemeinschaft Adipositas im Kindes- und Jugendalter (AGA). Bariatrisch-chirurgische Maßnahmen bei Jugendlichen mit extremer Adipositas. Monatsschr Kinderheilkd 2012; 160: 1123-1128 DOI: 10.1007/s00112-012-2749-7.
    CrossrefPubMedGoogle Scholar
  • 14 Wabitsch M, Schnurbein von J, Vollbach H. et al. Innovative medical care concepts for adolescents with severe obesity. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020; 63: 831-838 DOI: 10.1007/s00103-020-03167-y.
    CrossrefPubMedGoogle Scholar
  • 15 Farooqi IS, O'Rahilly S, Farooqi IS. Monogenic human obesity syndromes: Genetics of obesity. Handb Clin Neurol 2021; 181: 301-310 DOI: 10.1016/b978-0-12-820683-6.00022-1.
    CrossrefPubMedGoogle Scholar
  • 16 Huvenne H, Dubern B, Clément K. et al. Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016. Obes Facts 2016; 9: 158-173
    CrossrefPubMedGoogle Scholar
  • 17 Scheimann AO, Butler MG, Gourash L. et al. Critical analysis of bariatric procedures in Prader-Willi syndrome. J Pediatr Gastroenterol Nutr 2008; 46: 80-83
    CrossrefPubMedGoogle Scholar
  • 18 Lima VP, Emerich DR, Mesquita ML. et al. Nutritional intervention with hypocaloric diet for weight control in children and adolescents with Prader-Willi Syndrome. Eat Behav 2016; 21: 189-192 DOI: 10.1016/j.eatbeh.2016.03.008.
    CrossrefPubMedGoogle Scholar
  • 19 Vos N, Oussaada SM, Cooiman MI. et al. Bariatric Surgery for Monogenic Non-syndromic and Syndromic Obesity Disorders. Curr Diab Rep 2020; 20: 44
    CrossrefPubMedGoogle Scholar
  • 20 Reinehr T, Hebebrand J, Friedel S. et al. Lifestyle intervention in obese children with variations in the melanocortin 4 receptor gene. Obesity (Silver Spring) 2009; 17: 382-389 DOI: 10.1038/oby.2008.422.
    CrossrefPubMedGoogle Scholar
  • 21 Trier C, Hollensted M, Schnurr TM. et al. Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations. Int J Obes (Lond) 2021; 45: 66-76
    CrossrefPubMedGoogle Scholar
  • 22 Cooiman MI, Kleinendorst L, Aarts EO. et al. Genetic Obesity and Bariatric Surgery Outcome in 1014 Patients with Morbid Obesity. Obes Surg 2020; 30: 470-477 DOI: 10.1007/s11695-019-04184-w.
    CrossrefPubMedGoogle Scholar
  • 23 Drucker DJ, Habener JF, Holst JJ. Discovery, characterization, and clinical development of the glucagon-like peptides. J Clin Invest 2017; 127: 4217-4227
    CrossrefPubMedGoogle Scholar
  • 24 Turton MD, O'Shea D, Gunn I. et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379: 69-72 DOI: 10.1038/379069a0.
    CrossrefPubMedGoogle Scholar
  • 25 Secher A, Jelsing J, Baquero AF. et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest 2014; 124: 4473-4488
    CrossrefPubMedGoogle Scholar
  • 26 Gabery S, Salinas CG, Paulsen SJ. et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight 2020; 5: e133429 DOI: 10.1172/jci.insight.133429.
    CrossrefPubMedGoogle Scholar
  • 27 Abbott CR, Monteiro M, Small CJ. et al. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 2005; 1044: 127-131 DOI: 10.1016/j.brainres.2005.03.011.
    CrossrefPubMedGoogle Scholar
  • 28 Marso SP, Bain SC, Consoli A. et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375: 1834-1844 DOI: 10.1056/NEJMoa1607141.
    CrossrefPubMedGoogle Scholar
  • 29 Patel Chavez C, Cusi K, Kadiyala S. The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD. J Clin Endocrinol Metab 2022; 107: 29-38
    CrossrefPubMedGoogle Scholar
  • 30 Cena H, Chiovato L, Nappi RE. Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists. J Clin Endocrinol Metab 2020; 105: e2695-e2709
    CrossrefPubMedGoogle Scholar
  • 31 Kromeyer-Hauschild K, Wabitsch M, Kunze D. et al. Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschrift für Kinderheilkunde 2001; 149: 807-818
    CrossrefPubMedGoogle Scholar
  • 32 Brandt S, von Schnurbein J, Lennerz B. et al. Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI-SDS-A case series. Pediatr Obes 2020; 15: e12577 DOI: 10.1111/ijpo.12577.
    CrossrefPubMedGoogle Scholar
  • 33 Iepsen EW, Zhang J, Thomsen HS. et al. Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist. Cell Metab 2018; 28: 23-32 e23 DOI: 10.1016/j.cmet.2018.05.008.
    CrossrefPubMedGoogle Scholar
  • 34 Çamtosun E, Akıncı A, Kayaş L. et al. Liraglutide Treatment in a Morbidly Obese Adolescent with a MC4R Gene Variant: Side Effects Reduce Success. J Clin Res Pediatr Endocrinol 2023; 15: 225-229
    CrossrefPubMedGoogle Scholar
  • 35 Iepsen EW, Have CT, Veedfald S. et al. GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report. Cell Rep Med 2020; 1: 100006
    CrossrefPubMedGoogle Scholar
  • 36 Fojas EGF, Radha SK, Ali T. et al. Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency. Front Endocrinol (Lausanne) 2021; 12: 792354
    CrossrefPubMedGoogle Scholar
  • 37 Muratori F, Vignati F, Di Sacco G. et al. Efficacy of liraglutide 3.0 mg treatment on weight loss in patients with weight regain after bariatric surgery. Eat Weight Disord 2022; 27: 2775-2781 DOI: 10.1002/oby.23596.
    CrossrefPubMedGoogle Scholar
  • 38 Lundgren JR, Janus C, Jensen SBK. et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med 2021; 384: 1719-1730 DOI: 10.1056/NEJMoa2028198.
    CrossrefPubMedGoogle Scholar
  • 39 Trenson L, Trenson S, van Nes F. et al. Liraglutide for Weight Management in the Real World: Significant Weight Loss Even if the Maximal Daily Dose Is Not Achieved. Obes Facts 2022; 15: 83-89
    CrossrefPubMedGoogle Scholar
  • 40 Kelly AS, Arslanian S, Hesse D. et al. Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg. Obesity (Silver Spring) 2023; DOI: 10.1002/oby.23808.
    CrossrefPubMedGoogle Scholar
  • 41 Weghuber D, Barrett T, Barrientos-Pérez M. et al. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med 2022; 387: 2245-2257
    CrossrefPubMedGoogle Scholar
  • 42 Jastreboff AM, Aronne LJ, Ahmad NN. et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022; 387: 205-216 DOI: 10.1056/NEJMoa2206038.
    CrossrefPubMedGoogle Scholar
  • 43 Jastreboff AM, Kushner RF. New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics. Annu Rev Med 2023; 74: 125-139 DOI: 10.1146/annurev-med-043021-014919.
    CrossrefPubMedGoogle Scholar
  • 44 Mali G, Ahuja V, Dubey K. Glucagon-like peptide-1 analogues and thyroid cancer: An analysis of cases reported in the European pharmacovigilance database. J Clin Pharm Ther 2021; 46: 99-105 DOI: 10.1111/jcpt.13259.
    CrossrefPubMedGoogle Scholar
  • 45 Bezin J, Gouverneur A, Pénichon M. et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care 2023; 46: 384-390 DOI: 10.2337/dc22-1148.
    CrossrefPubMedGoogle Scholar
  • 46 Elashoff M, Matveyenko AV, Gier B. et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011; 141: 150-156
    CrossrefPubMedGoogle Scholar
  • 47 Yang Z, Lv Y, Yu M. et al. GLP-1 receptor agonist-associated tumor adverse events: A real-world study from 2004 to 2021 based on FAERS. Front Pharmacol 2022; 13: 925377 DOI: 10.3389/fendo.2021.645563.
    CrossrefPubMedGoogle Scholar
  • 48 Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med 2008; 358: 1970-1971
    PubMedGoogle Scholar
  • 49 Gier B, Matveyenko AV, Kirakossian D. et al. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras (G12D) mouse model. Diabetes 2012; 61: 1250-1262
    CrossrefPubMedGoogle Scholar
  • 50 Monami M, Nreu B, Scatena A. et al. Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): Data from randomized controlled trials. Diabetes Obes Metab 2017; 19: 1233-1241 DOI: 10.1111/dom.12926.
    CrossrefPubMedGoogle Scholar
  • 51 He L, Wang J, Ping F. et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med 2022; 182: 513-519
    CrossrefPubMedGoogle Scholar
  • 52 Piccoli GF, Mesquita LA, Stein C. et al. Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis. J Clin Endocrinol Metab 2021; 106: 912-921 DOI: 10.1210/clinem/dgaa891.
    CrossrefPubMedGoogle Scholar