Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

ERS Congress 2024

Keep up to date on the latest news from the annual European Respiratory Society conference.
ADVANCED SEARCH
Log in
Top
Current Pediatrics Reports

20-08-2024 | Pediatric Obesity Free for a limited time

Second Generation Anti-Obesity Medications

Authors: Sri Nikhita Chimatapu, Steven D. Mittelman, Vibha Singhal

Published in: Current Pediatrics Reports

Login to get access

Abstract

Purpose of Review

This review aims to synthesize recent advancements in the pharmacological management of pediatric obesity, highlighting second generation anti-obesity medications and focusing on their efficacy, safety and impact on metabolic outcomes in children and adolescents.

Recent Findings

Significant progress has been made in the treatment of pediatric obesity through the introduction of second-generation anti-obesity medications. These have shown promising results in reducing body mass index (BMI) in adolescents. They represent a shift towards more, mechanistic approaches in treating pediatric obesity and producing effect sizes that were previously not possible with available pharmacotherapy. Also, the newer medications have more pleiotropic benefits.

Summary

Pediatric obesity treatment is witnessing significant evolution with the introduction of second-generation anti-obesity medications and novel therapeutic strategies. As the field progresses, more effective, personalized, and safer treatment options promise to enhance the quality of life and health outcomes for children and adolescents struggling with obesity. The integration of these advanced pharmacotherapies into ongoing lifestyle interventions represents a key factor in the holistic and effective approach to managing this complex and increasingly prevalent condition.
Literature
1.
2.
Badesha HS, Bagri G, Nagra A, Nijran K, Singh G, Aiyegbusi OL. Tackling childhood overweight and obesity after the COVID-19 pandemic. Lancet Child Adolesc Health. 2021;5(10):687–8.PubMedPubMedCentralCrossRef
3.
The Lancet Public H. Childhood obesity beyond COVID-19. Lancet Public Health. 2021;6(8):e534.CrossRef
4.
Force USPST, Grossman DC, Bibbins-Domingo K, Curry SJ, Barry MJ, Davidson KW, et al. Screening for obesity in children and adolescents: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;317(23):2417–26.CrossRef
5.
Skinner AC, Ravanbakht SN, Skelton JA, Perrin EM, Armstrong SC. Prevalence of obesity and severe obesity in US children, 1999–2016. Pediatrics. 2018;141(3):e20173459.PubMedCrossRef
6.
Okunogbe A, Nugent R, Spencer G, Powis J, Ralston J, Wilding J. Economic impacts of overweight and obesity: current and future estimates for 161 countries. BMJ Glob Health. 2022;7(9).
7.
Estrada E, Eneli I, Hampl S, Mietus-Snyder M, Mirza N, Rhodes E, et al. Children’s Hospital Association consensus statements for comorbidities of childhood obesity. Child Obes. 2014;10(4):304–17.PubMedPubMedCentralCrossRef
8.
Expert Panel on Integrated Guidelines for Cardiovascular, Heart H, Blood L. I. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 Suppl 5(Suppl 5):S213-56.
9.
Twig G, Reichman B, Afek A, Derazne E, Hamiel U, Furer A, et al. Severe obesity and cardio-metabolic comorbidities: a nationwide study of 2.8 million adolescents. Int J Obes (Lond). 2019;43(7):1391–9.PubMedCrossRef
10.
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.PubMedCrossRef
11.
Sanyaolu A, Okorie C, Qi X, Locke J, Rehman S. Childhood and adolescent obesity in the United States: a Public Health concern. Glob Pediatr Health. 2019;6:2333794X19891305.PubMedPubMedCentral
12.
Skelton JA, Cook SR, Auinger P, Klein JD, Barlow SE. Prevalence and trends of severe obesity among US children and adolescents. Acad Pediatr. 2009;9(5):322–9.PubMedPubMedCentralCrossRef
13.
Hampl SE, Hassink SG, Skinner AC, Armstrong SC, Barlow SE, Bolling CF et al. Clinical practice Guideline for the evaluation and treatment of children and adolescents with obesity. Pediatrics. 2023;151(2).
14.
15.
Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O’Malley C, Stolk RP, et al. Interventions for treating obesity in children. Cochrane Database of Systematic Reviews; 2009.
16.
17.
Stigler FL, Lustig RH, Ma JI. Mechanisms, pathophysiology, and management of obesity. N Engl J Med. 2017;376(15):1491.PubMed
18.
Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;11(11):CD012436.PubMed
19.
20.
Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, et al. A Randomized, Controlled Trial of Liraglutide for adolescents with obesity. N Engl J Med. 2020;382(22):2117–28.PubMedCrossRef
21.
Clement K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, et al. 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):960–70.PubMedCrossRef
22.
Weghuber D, Barrett T, Barrientos-Perez M, Gies I, Hesse D, Jeppesen OK, et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med. 2022;387(24):2245–57.PubMedPubMedCentralCrossRef
23.
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like Peptide-1. Cell Metab. 2018;27(4):740–56.PubMedCrossRef
24.
Farr OM, Tsoukas MA, Triantafyllou G, Dincer F, Filippaios A, Ko BJ, et al. Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: a randomized, placebo-controlled, crossover study. Metabolism. 2016;65(7):945–53.PubMedPubMedCentralCrossRef
25.
Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004;287(2):E199–206.PubMedCrossRef
26.
Maselli DB, Camilleri M. Effects of GLP-1 and its analogs on gastric physiology in diabetes Mellitus and obesity. Adv Exp Med Biol. 2021;1307:171–92.PubMedCrossRef
27.
Lopes KG, da Silva VLJ, de Azevedo Marques Lopes F, Bouskela E, Coelho de Souza MDG, Kraemer-Aguiar LG. Ghrelin and glucagon-like peptide-1 according to body adiposity and glucose homeostasis. Arch Endocrinol Metab. 2023;67(4):e000611.PubMedPubMedCentralCrossRef
28.
29.
Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998;47(11):1663–70.PubMedCrossRef
30.
Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373(9662):473–81.PubMedCrossRef
31.
Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571–8.PubMedCrossRef
32.
33.
Kuhnen P, Clement K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, et al. Proopiomelanocortin Deficiency treated with a Melanocortin-4 receptor agonist. N Engl J Med. 2016;375(3):240–6.PubMedCrossRef
34.
Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085–95.PubMedCrossRef
35.
Greenfield JR, Miller JW, Keogh JM, Henning E, Satterwhite JH, Cameron GS, et al. Modulation of blood pressure by central melanocortinergic pathways. N Engl J Med. 2009;360(1):44–52.PubMedCrossRef
36.
Lonneman DJ Jr., Rey JA, McKee BD. Phentermine/Topiramate extended-release capsules (qsymia) for weight loss. P T. 2013;38(8):446–52.PubMedPubMedCentral
37.
38.
Picard F, Deshaies Y, Lalonde J, Samson P, Richard D. Topiramate reduces energy and fat gains in lean (Fa/?) And obese (fa/fa) Zucker rats. Obes Res. 2000;8(9):656–63.PubMedCrossRef
39.
Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–52.PubMedCrossRef
40.
Hsia DS, Gosselin NH, Williams J, Farhat N, Marier JF, Shih W, et al. A randomized, double-blind, placebo-controlled, pharmacokinetic and pharmacodynamic study of a fixed-dose combination of phentermine/topiramate in adolescents with obesity. Diabetes Obes Metab. 2020;22(4):480–91.PubMedCrossRef
41.
Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392(10160):2180–93.PubMedCrossRef
42.
Avgerinos I, Kakotrichi P, Karagiannis T, Bekiari E, Tsapas A. The preclinical discovery and clinical evaluation of tirzepatide for the treatment of type 2 diabetes. Expert Opin Drug Discov. 2024;19(5):511–22.PubMedCrossRef
43.
Lv X, Wang H, Chen C, Zhao Y, Li K, Wang Y, et al. The Effect of Tirzepatide on Weight, lipid metabolism and blood pressure in Overweight/Obese patients with type 2 diabetes Mellitus: a systematic review and Meta-analysis. Diabetes Metab Syndr Obes. 2024;17:701–14.PubMedPubMedCentralCrossRef
44.
Kuhnen P, Wabitsch M, von Schnurbein J, Chirila C, Mallya UG, Callahan P, et al. Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency. Orphanet J Rare Dis. 2022;17(1):38.PubMedPubMedCentralCrossRef
45.
Haqq AM, Chung WK, Dollfus H, Haws RM, Martos-Moreno GA, Poitou C, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022;10(12):859–68.PubMedPubMedCentralCrossRef
46.
Kelly AS, Bensignor MO, Hsia DS, Shoemaker AH, Shih W, Peterson C et al. Phentermine/Topiramate for the Treatment of Adolescent Obesity. NEJM Evid. 2022;1(6).
47.
Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, et al. Tirzepatide versus Semaglutide once Weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–15.PubMedCrossRef
48.
Andersen A, Lund A, Knop FK, Vilsboll T. Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol. 2018;14(7):390–403.PubMedCrossRef
49.
50.
51.
Wang JY, Wang QW, Yang XY, Yang W, Li DR, Jin JY, et al. GLP-1 receptor agonists for the treatment of obesity: role as a promising approach. Front Endocrinol (Lausanne). 2023;14:1085799.PubMedCrossRef
52.
Allison KC, Chao AM, Bruzas MB, McCuen-Wurst C, Jones E, McAllister C, et al. A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder. Obes Sci Pract. 2023;9(2):127–36.PubMedCrossRef
53.
Liu W, Wang Z, Wang W, Wang Z, Xing Y, Holscher C. Liraglutide reduces alcohol consumption, anxiety, memory impairment, and synapse loss in Alcohol Dependent mice. Neurochem Res. 2024;49(4):1061–75.PubMedCrossRef
54.
Kanbay M, Copur S, Siriopol D, Yildiz AB, Gaipov A, van Raalte DH, et al. Effect of tirzepatide on blood pressure and lipids: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2023;25(12):3766–78.PubMedCrossRef
55.
Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024.
56.
57.
Stephens JW, Bain SC. Safety and adverse effects associated with GLP-1 analogues. Expert Opin Drug Saf. 2007;6(4):417–22.PubMedCrossRef
58.
Feier CVI, Vonica RC, Faur AM, Streinu DR, Muntean C. Assessment of thyroid carcinogenic risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and obesity: a systematic literature review. Int J Mol Sci. 2024;25(8).
59.
Shin JH, Gadde KM. Clinical utility of phentermine/topiramate (Qsymia) combination for the treatment of obesity. Diabetes Metab Syndr Obes. 2013;6:131–9.PubMedPubMedCentral
60.
Chakhtoura M, Haber R, Ghezzawi M, Rhayem C, Tcheroyan R, Mantzoros CS. Pharmacotherapy of obesity: an update on the available medications and drugs under investigation. EClinicalMedicine. 2023;58:101882.PubMedPubMedCentralCrossRef
61.
Elliott JP, Gray EL, Yu J, Kalarchian MA. Medication use among patients prior to bariatric surgery. Bariatr Surg Pract Patient Care. 2015;10(3):105–9.PubMedPubMedCentralCrossRef
62.
Heymsfield SB, Coleman LA, Miller R, Rooks DS, Laurent D, Petricoul O, et al. Effect of Bimagrumab vs Placebo on Body Fat Mass among adults with type 2 diabetes and obesity. JAMA Netw Open. 2021;4(1):e2033457.PubMedPubMedCentralCrossRef
63.
Jastreboff AM, Kaplan LM, Frias JP, Wu Q, Du Y, Gurbuz S, et al. Triple-hormone-receptor agonist retatrutide for obesity - A phase 2 trial. N Engl J Med. 2023;389(6):514–26.PubMedCrossRef
64.
65.
Allas S, Caixas A, Poitou C, Coupaye M, Thuilleaux D, Lorenzini F, et al. AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with prader-Willi syndrome: a randomized placebo-controlled trial. PLoS ONE. 2018;13(1):e0190849.PubMedPubMedCentralCrossRef
66.
Becerril S, Fruhbeck G. Cagrilintide plus Semaglutide for obesity management. Lancet. 2021;397(10286):1687–9.PubMedCrossRef
67.
McCormack SE, Wang Z, Wade KL, Dedio A, Cilenti N, Crowley J, et al. A pilot randomized clinical trial of Intranasal Oxytocin to promote weight loss in individuals with hypothalamic obesity. J Endocr Soc. 2023;7(5):bvad037.PubMedPubMedCentralCrossRef
68.
Pont SJ, Puhl R, Cook SR, Slusser W, Section On O, Obesity S. Stigma experienced by children and adolescents with obesity. Pediatrics. 2017;140(6).
69.
Sargeant JA, Henson J, King JA, Yates T, Khunti K, Davies MJ. A review of the effects of Glucagon-Like Peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors on lean body Mass in humans. Endocrinol Metab (Seoul). 2019;34(3):247–62.PubMedCrossRef
70.
Lerch MF, Thrane SE. Adolescents with chronic illness and the transition to self-management: a systematic review. J Adolesc. 2019;72:152–61.PubMedCrossRef
71.
Iughetti L, China M, Berri R, Predieri B. Pharmacological treatment of obesity in children and adolescents: present and future. J Obes. 2011;2011:928165.PubMedCrossRef
72.
Keller M, Svensson SIA, Rohde-Zimmermann K, Kovacs P, Bottcher Y. Genetics and epigenetics in obesity: what do we know so far? Curr Obes Rep. 2023;12(4):482–501.PubMedPubMedCentralCrossRef
73.
Whitlock EP, O’Connor EA, Williams SB, Beil TL, Lutz KW. Effectiveness of weight management interventions in children: a targeted systematic review for the USPSTF. Pediatrics. 2010;125(2):e396–418.PubMedCrossRef
74.
Vine M, Hargreaves MB, Briefel RR, Orfield C. Expanding the role of primary care in the prevention and treatment of childhood obesity: a review of clinic- and community-based recommendations and interventions. J Obes. 2013;2013:172035.PubMedPubMedCentralCrossRef
Metadata
Title
Second Generation Anti-Obesity Medications
Authors
Sri Nikhita Chimatapu
Steven D. Mittelman
Vibha Singhal
Publication date
20-08-2024
Publisher
Springer US
Published in
Current Pediatrics Reports
Electronic ISSN: 2167-4841
DOI
https://doi.org/10.1007/s40124-024-00326-6
Image Credits