Current pharmacotherapy options in pediatric obesity
Authors:
Malíková Křenek Jana 1; Hainerová Aldhoon Irena 2,3; Lebl Jan 1
Authors place of work:
Pediatrická klinika, 2. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice v Motole, Praha
1; Klinika dětí a dorostu, 3. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Královské Vinohrady, Praha
2; Pediatrická klinika, 1. lékařská fakulta Univerzity Karlovy a Fakultní Thomayerovy nemocnice, Praha
3
Published in the journal:
Čes-slov Pediat 2023; 78 (2): 122-126.
Category:
Childhood Obesity Epidemic
doi:
https://doi.org/10.55095/CSPediatrie2023/017
Summary
Obesity is a serious chronic condition that requires a comprehensive multidisciplinary approach. The main components of obesity treatment are education towards healthy eating habits, increased physical activity, decreased sedentarism and regular sleep pattern. Excess body weight is often associated with psychopathological behavior. Children often present with sadness, depression, low self-esteem, and therefore the role of psychotherapy or cognitive behavioral therapy is highly important in the complex approach to the treatment of childhood obesity. In recent years, the use of pharmacotherapy, both targeted for the treatment of certain genetic disorders and for the treatment of polygenic obesity, has significantly expanded. Three drugs are currently approved for use in children. These are metreleptin for genetically confirmed leptin deficiency, and setmelanotide, which is used in individuals with pathogenic variants of genes encoding leptin receptor, proopiomelanocortin or proprotein convertase genes, and in patients with Bardet-Biedl syndrome. Other types of obesity may benefit from treatment with liraglutide, which is a glucagon-like peptide 1 analogue. Obesity research is ongoing, and new molecules and their combinations that may be complementary in a comprehensive approach to obesity treatment can be expected.
Keywords:
obesity – leptin – liraglutide – pharmacotherapy – glucagon-like peptide 1 – metreleptin – setmelanotide
Zdroje
1. Wijga AH, Mohnen SM, Vonk JM, Uiters E. Healthcare utilisation and expenditure of overweight and non-overweight children. J Epidemiol Community Health 2018; 72(10): 940–943.
2. van de Pas KGH, Lubrecht JW, Hesselink ML, et al. The effect of a multidisciplinary lifestyle intervention on health parameters in children versus adolescents with severe obesity. Nutrients 2022; 14(9): 1795.
3. Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al.; Ellipse Trial Investigators. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med 2019; 381(7): 637–646.
4. Lebl J, Křenek Malíkova J, Aldhoon Hainerová I. Regulace energetické rovnováhy a jídelního chování. Ces-slov Pediat 2023; 78(1): 48–53.
5. Paz-Filho G, Mastronardi CA, Licinio J. Leptin treatment: facts and expectations. Metabolism. 2015; 64(1): 146–56.
6. Matochik JA, London ED, Yildiz BO, et al. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab. 2005; 90(5): 2851–4.
7. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341(12): 879–84.
8. Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110(8): 1093– 103.
9. E ihara K, Kusakabe T, Hirata M, et al. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab 2007; 92(2): 532–41.
10. Meehan CA, Cochran E, Kassai A, et al. Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Expert Rev Clin Pharmacol 2016; 9(1): 59– 68.
11. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351(10): 987–97.
12. Chou SH, Chamberland JP, Liu X, et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci U S A 2011; 108(16): 6585– 90.
13. Zelissen PM, Stenlof K, Lean ME, et al.; Author Group. Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial. Diabetes Obes Metab 2005; 7(6): 755–61.
14. Collet TH, Dubern B, Mokrosinski J, et al. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Mol Metab 2017; 6(10): 1321–1329.
15. Clément K, van den Akker E, Argente J, et al.; Setmelanotide POMC and LEPR Phase 3 Trial Investigators. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020; 8(12): 960–970.
16. Haqq AM, Chung WK, Dollfus H, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo- -controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol 2022; 10(12): 859–868.
17. Hinney A, Körner A, Fischer-Posovszky P. The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits. Nat Rev Endocrinol 2022; 18(10): 623–637.
18. Kanti V, Puder L, Jahnke I, et al. A melanocortin-4 receptor agonist induces skin and hair pigmentation in patients with monogenic mutations in the leptin- melanocortin pathway. Skin Pharmacol Physiol 2021; 34(6): 307–316.
19. Tagliabue E, Gandini S, Bellocco R, et al. MC1R variants as melanoma risk factors independent of at-risk phenotypic characteristics: a pooled analysis from the M-SKIP project. Cancer Manag Res 2018; 10: 1143–1154.
20. Orskov C, Wettergren A, Holst JJ. Secretion of the incretin hormones glucagon- like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol 1996; 31(7): 665–70.
21. Mojsov S, Heinrich G, Wilson IB, et al. Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem 1986; 261(25): 11880–9.
22. Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007; 48(5): 736–43.
23. Baggio LL, Yusta B, Mulvihill EE, et al. GLP-1 Receptor Expression Within the Human Heart. Endocrinology. 2018; 159(4): 1570–1584.
24. Drucker DJ, Philippe J, Mojsov S, et al. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A 1987; 84(10): 3434–8.
25. Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet 1987; 330: 1300–1304.
26. Cornu M, Thorens B. GLP-1 protects beta-cells against apoptosis by enhancing the activity of an IGF-2/IGF1-receptor autocrine loop. Islets 2009; 1: 280–282.
27. Perfetti R, Hui H. The role of GLP-1 in the life and death of pancreatic beta cells. Horm Metab Res 2004; 36(11–12): 804–10.
28. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997; 273(5): E981–8.
29. 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(6560): 69–72.
30. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101(3): 515–20.
31. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375(4): 311–22.
32. Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993; 214(3): 829–35.
33. Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon- like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000; 43(9): 1664–9.
34. Kelly AS, Auerbach P, Barrientos-Perez M, et al.; NN8022-4180 Trial Investigators. A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med 2020; 382(22): 2117–2128.
35. Hu W, Song R, Cheng R, et al. Use of GLP-1 receptor agonists and occurrence of thyroid disorders: a meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne) 2022; 13: 927859.
36. Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study Group. Once- -weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021; 384(11): 989–1002.
37. Weghuber D, Barrett T, Barrientos-Pérez M, et al.; STEP TEENS Investigators. Once-weekly semaglutide in adolescents with obesity. N Engl J Med 2022; 387(24): 2245–2257.
38. M üller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov 2022; 21(3): 201–223.
39. Hainer V, Kunešová M, Taxová Braunerova R, Aldhoon Hainerová I. Duální agonista inkretinových receptorů tirzepatid: Nové antidiabetikum je nadějnou perspektivou v léčbě obezity. DMEV 2022; 25(4): 136–140.
Štítky
Neonatology Paediatrics General practitioner for children and adolescentsČlánok vyšiel v časopise
Czech-Slovak Pediatrics
2023 Číslo 2
- What Effect Can Be Expected from Limosilactobacillus reuteri in Mucositis and Peri-Implantitis?
- The Importance of Limosilactobacillus reuteri in Administration to Diabetics with Gingivitis
Najčítanejšie v tomto čísle
- Myocarditis and cardiomyopathy
- Preparation of the child for the magnetic resonance examination
- Prenatal diagnosis of ovarian cysts, management and pregnancy outcomes
- Current pharmacotherapy options in pediatric obesity