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At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
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Current Obesity Reports

30-04-2024 | Obesity | REVIEW

Update on Pediatric Anti-obesity Medications—Current Landscape and Approach to Prescribing

Authors: Yoon Ji Ahn, Jacqueline Maya, Vibha Singhal

Published in: Current Obesity Reports

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Abstract

Purpose of Review

To review the current medical therapies available for treatment of obesity in children and adolescents less than 18 years old in the United States and outline the approach to their use.

Recent Findings

Obesity is a chronic disease with increasing prevalence in children and adolescents in the United States. Over the past few years, more FDA-approved medical treatments for obesity, such as GLP-1 receptor agonists, have emerged for patients less than 18 years old. Furthermore, there are medications with weight loss effects that can be used off-label for obesity in pediatric patients. However, access to many of these medications is limited due to age restrictions, insurance coverage, and cost.

Summary

Medical options are improving to provide treatment for obesity in pediatric populations. FDA and off-label medications should be considered when appropriate to treat children and adolescents with obesity. However, further studies are needed to evaluate the efficacy and long-term safety of FDA-approved and off-label medications for obesity treatment in pediatric patients.
Literature
1.
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): e2022060640.PubMedCrossRef
2.
Zhao G, Zhang Q, Wu F, Yin S, Xie Y, Liu H. Comparison of weight loss and adverse events of obesity drugs in children and adolescents: a systematic review and meta-analysis. Expert Rev Clin Pharmacol. 2022;15(9):1119–25.PubMedCrossRef
3.
Hvizdos KM, Markham A. Orlistat: a review of its use in the management of obesity. Drugs. 1999;58(4):743–60.PubMedCrossRef
4.
Orlistat [package insert]. Nutley (NJ): Roche laboratories, Inc; 1999.
5.
Ozkan B, Bereket A, Turan S, Keskin S. Addition of orlistat to conventional treatment in adolescents with severe obesity. Eur J Pediatr. 2004;163(12):738–41.PubMedCrossRef
6.
Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA. 2005;293(23):2873.PubMedCrossRef
7.
Maahs D, de Serna DG, Kolotkin RL, Ralston S, Sandate J, Qualls C, et al. Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocr Pract. 2006;12(1):18–28.PubMedCrossRef
8.
Jackson IMD, Whyte WG. Chlorphentermine S.A. in the treatment of obesity and the effect of weight loss on steroid excretion. BMJ. 1965;2(5459):453–5.PubMedPubMedCentralCrossRef
9.
Ryder JR, Kaizer A, Rudser KD, Gross A, Kelly AS, Fox CK. Effect of phentermine on weight reduction in a pediatric weight management clinic. Int J Obes. 2017;41(1):90–3.CrossRef
10.
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
11.
•• Kelly AS, Bensignor MO, Hsia DS, Shoemaker AH, Shih W, Peterson C, Varghese ST. Phentermine/topiramate for the treatment of adolescent obesity. NEJM Evid. 2022;1(6):10. https://​doi.​org/​10.​1056/​evidoa2200014. Phentermine/topiramate has not previously been examined for efficacy and safety in a major randomized controlled trial in adolescents. With GLP-1 receptor agonist shortages, prescribers’ abilities and comfort levels to prescribe other AOMs is vital.
12.
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
13.
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.PubMedPubMedCentralCrossRef
14.
Schlögl H, Kabisch S, Horstmann A, Lohmann G, Müller K, Lepsien J, et al. Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity. Diabetes Care. 2013;36(7):1933–40.PubMedPubMedCentralCrossRef
15.
• 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.  This trial demonstrates the efficacy of using a daily GLP-1 receptor agonist.PubMedCrossRef
16.
• Weghuber D, Barrett T, Barrientos-Pérez 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. This trial was important in demonstrating efficacy of a weekly GLP-1 receptor agonist in adolescents to then lead to FDA approval for adolescent use.PubMedPubMedCentralCrossRef
17.
Kühnen P, Clément 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
18.
Kühnen P, Clément K. Long-term MC4R agonist treatment in POMC-deficient patients. N Engl J Med. 2022;387(9):852–4.PubMedCrossRef
19.
Clément K, Biebermann H, Farooqi IS, Van der Ploeg L, Wolters B, Poitou C, et al. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nat Med. 2018;24(5):551–5.PubMedCrossRef
20.
Clément 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
21.
Haqq AM, Chung WK, Dollfus H, Haws RM, Martos-Moreno GÁ, Poitou C, 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):859–68.PubMedPubMedCentralCrossRef
22.
Okuyaz CMD, Kursel OMD, Komur MMD, Tamer LMD. Evaluation of appetite-stimulating hormones in prepubertal children with epilepsy during topiramate treatment. Pediatr Neurol. 2012;47(6):423–6.PubMedCrossRef
23.
McElroy SL, Hudson JI, Capece JA, Beyers K, Fisher AC, Rosenthal NR. Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study. Biol Psychiatry 1969. 2007;61(9):1039–48.
24.
Zheng H, Patterson C, Berthoud HR. Behavioral analysis of anorexia produced by hindbrain injections of AMPA receptor antagonist NBQX in rats. Am J Physiol-Regul Integr Comp Physiol. 2002;282(1):R147–55.PubMedCrossRef
25.
26.
Fox CK, Marlatt KL, Rudser KD, Kelly AS. Topiramate for weight reduction in adolescents with severe obesity. Clin Pediatr (Phila). 2015;54(1):19–24.PubMedCrossRef
27.
Fox CK, Kaizer AM, Rudser KD, Nathan BM, Gross AC, Sunni M, et al. Meal replacements followed by topiramate for the treatment of adolescent severe obesity: a pilot randomized controlled trial. Obesity. 2016;24(12):2553–61.PubMedCrossRef
28.
Khazaal YMD, Chatton AMA, Rusca MBA, Preisig MMD, Zullino DMD. Long-term topiramate treatment of psychotropic drug-induced weight gain: a retrospective chart review. Gen Hosp Psychiatry. 2007;29(5):446–9.PubMedCrossRef
29.
Wang C, Shi W, Xu J, Huang C, Zhu J. Outcomes and safety of concomitant topiramate or metformin for antipsychotics-induced obesity: a randomized-controlled trial. Ann Gen Psychiatry. 2020;19:1–10.CrossRef
30.
31.
Mulherin AJ, Oh AH, Kim H, Grieco A, Lauffer LM, Brubaker PL. Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell. Endocrinology. 2011;152(12):4610–9.PubMedCrossRef
32.
DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, et al. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016;59(8):1645–54.PubMedPubMedCentralCrossRef
33.
Ford JL, Gerhart JG, Edginton AN, Yanovski JA, Hon YY, Gonzalez D. Physiologically based pharmacokinetic modeling of metformin in children and adolescents with obesity. J Clin Pharmacol. 2022;62(8):960–9.PubMedPubMedCentralCrossRef
34.
McDonagh MS, Selph S, Ozpinar A, Foley C. Systematic review of the benefits and risks of metformin in treating obesity in children aged 18 years and younger. JAMA Pediatr. 2014;168(2):178–84.PubMedCrossRef
35.
Carreras-Badosa G, Gómez-Vilarrubla A, Mas-Parés B, Martínez-Calcerrada JM, Xargay-Torrent S, Prats-Puig A, et al. A 24-month metformin treatment study of children with obesity: changes in circulating GDF-15 and associations with changes in body weight and visceral fat. Pediatr Obes. 2022;17(2): e12845.PubMedCrossRef
36.
Concepcion JQ, Tucker LY, Huang K. Metformin for pediatric obesity and insulin resistance: a retrospective study within an integrated health care system. Obesity. 2021;29(9):1526–37.PubMedCrossRef
37.
Asanka de Silva V, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16(1):341.CrossRef
38.
Ermer JC, Pennick M, Frick G. Lisdexamfetamine dimesylate: prodrug delivery, amphetamine exposure and duration of efficacy. Clin Drug Investig. 2016;36(5):341–56.PubMedPubMedCentralCrossRef
39.
Guerdjikova AI, Blom TJ, Mori N, Matthews A, Cummings T, Casuto LL, et al. Lisdexamfetamine in pediatric binge eating disorder: a retrospective chart review. Clin Neuropharmacol. 2019;42(6):214–6.PubMedCrossRef
40.
Banaschewski T, Johnson M, Nagy P, Otero IH, Soutullo CA, Yan B, et al. Growth and puberty in a 2-year open-label study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder. CNS Drugs. 2018;32(5):455–67.PubMedPubMedCentralCrossRef
41.
Greig SL, Keating GM. Naltrexone ER/bupropion ER: a review in obesity management. Drugs. 2015;75(11):1269–80.PubMedCrossRef
42.
Billes SK, Greenway FL. Combination therapy with naltrexone and bupropion for obesity. Expert Opin Pharmacother. 2011;12(11):1813–26.PubMedCrossRef
43.
Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature. 2006;443(7109):289–95.PubMedCrossRef
44.
White MA, Grilo CM. Bupropion for overweight women with binge eating disorder: randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2013;74(4):400–6.PubMedPubMedCentralCrossRef
45.
Grilo CM, Lydecker JA, Morgan PT, Gueorguieva R. Naltrexone + bupropion combination for the treatment of binge-eating disorder with obesity: a randomized, controlled pilot study. Clin Ther. 2021;43(1):112-122.e1.PubMedCrossRef
46.
Prof GFL, Fujioka KMD, Prof PRA, Prof MS, Guttadauria MMD, PhD EJ, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Br Ed. 2010;376(9741):595–605.CrossRef
47.
Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O’Neil PM, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011;19(1):110–20.PubMedCrossRef
48.
Hollander P, Gupta AK, Plodkowski R, Greenway F, Bays H, Burns C, et al. Effects of naltrexone sustained- release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36(12):4022–9.PubMedPubMedCentralCrossRef
49.
Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obes Silver Spring Md. 2013;21(5):935–43.CrossRef
50.
Arslanian SA, Hannon T, Zeitler P, Chao LC, Boucher-Berry C, Barrientos-Pérez M, et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022;387(5):433–43.PubMedCrossRef
51.
52.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205–16.PubMedCrossRef
53.
Adams TD, Davidson LE, Litwin SE, Kim J, Kolotkin RL, Nanjee MN, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377(12):1143–55.PubMedPubMedCentralCrossRef
54.
Heinberg LJ, Bond DS, Carroll I, Crosby R, Fodor A, Fouladi F, et al. Identifying mechanisms that predict weight trajectory after bariatric surgery: rationale and design of the biobehavioral trial. Surg Obes Relat Dis. 2020;16(11):1816–26.PubMedPubMedCentralCrossRef
55.
El Ansari W, Elhag W. Weight regain and insufficient weight loss after bariatric surgery: definitions, prevalence, mechanisms, predictors, prevention and management strategies, and knowledge gaps—a scoping review. Obes Surg. 2021;31(4):1755–66.PubMedPubMedCentralCrossRef
56.
Inge TH, Courcoulas AP, Jenkins TM, Michalsky MP, Helmrath MA, Brandt ML, et al. Weight loss and health status 3 years after bariatric surgery in adolescents. N Engl J Med. 2016;374(2):113–23.PubMedCrossRef
57.
Inge TH, Courcoulas AP, Jenkins TM, Michalsky MP, Brandt ML, Xanthakos SA, et al. Five-year outcomes of gastric bypass in adolescents as compared with adults. N Engl J Med. 2019;380(22):2136–45.PubMedPubMedCentralCrossRef
58.
Istfan NW, Anderson WA, Hess DT, Yu L, Carmine B, Apovian CM. The mitigating effect of phentermine and topiramate on weight regain after Roux-en-Y gastric bypass surgery. Obesity. 2020;28(6):1023–30.PubMedCrossRef
59.
Murvelashvili N, Xie L, Schellinger JN, Mathew MS, Marroquin EM, Lingvay I, et al. Effectiveness of semaglutide versus liraglutide for treating post-metabolic and bariatric surgery weight recurrence. Obesity. 2023;31(5):1280–9.PubMedCrossRef
60.
61.
Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514–26. Available from: https://​doi.​org/​10.​1056/​NEJMoa2301972.PubMedCrossRef
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: a phase 2 randomized clinical trial. JAMA Netw Open. 2021;4(1): e2033457.PubMedPubMedCentralCrossRef
63.
Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389(10):877–88.PubMedCrossRef
64.
Lawson EA, Olszewski PK, Weller A, Blevins JE. The role of oxytocin in regulation of appetitive behavior, body weight and glucose homeostasis. J Neuroendocrinol. 2020;32(4): e12805.PubMedCrossRef
65.
66.
67.
Weir MA, Beyea MM, Gomes T, Juurlink DN, Mamdani M, Blake PG, et al. Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med. 2011;171(7):703–4.PubMedCrossRef
68.
Srivastava G, Fox CK, Kelly AS, Jastreboff AM, Browne AF, Browne NT, et al. Clinical considerations regarding the use of obesity pharmacotherapy in adolescents with obesity. Obesity. 2019;27(2):190–204.PubMedCrossRef
69.
Phentermine [package insert]. Sellersville (PA): Teva Pharmaceuticals USA; 1959.
70.
Qsymia [package insert]. Winchester (KY): Catalent Pharma Solutions, LLC; 2012.
71.
Saxenda [package insert]. Plainsboro (NJ): Novo Nordisk Inc; 2014.
72.
Wegovy [package insert]. Plainsboro (NJ): Novo Nordisk Inc; 2022.
73.
Bjerre Knudsen L, Madsen LW, Andersen S, Almholt K, De Boer AS, Drucker DJ, et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010;151(4):1473–86.PubMedCrossRef
74.
Bezin J, Gouverneur A, Pénichon M, Mathieu C, Garrel R, Hillaire-Buys D, et al. GLP-1 receptor agonists and the risk of thyroid cancer. Diabetes Care. 2023;46(2):384–90.PubMedCrossRef
75.
Imcivree [package insert]. Boston (MA): Rhythm pharmaceuticals, Inc; 2020.
76.
Glucophage [package insert]. Princeton (NJ): Bristol-Myers Squibb Company; 2000.
77.
Pastor-Villaescusa B, Cañete MD, Caballero-Villarraso J, Hoyos R, Latorre M, Vázquez-Cobela R, et al. Metformin for obesity in prepubertal and pubertal children: a randomized controlled trial. Pediatrics. 2017;140(1): e20164285.PubMedCrossRef
78.
Masarwa R, Brunetti VC, Aloe S, Henderson M, Platt RW, Filion KB. Efficacy and safety of metformin for obesity: a systematic review. Pediatrics. 2021;147(3): e20201610.PubMedCrossRef
79.
Topiramate [package insert]. Titusville (NJ): Janssen Pharmaceuticals, Inc; 1996.
80.
Vyvanse [package insert]. Lexington (MA): Shire US Inc; 2007.
81.
Contrave [package insert]. Deerfield (IL): Takeda Pharmaceuticals America, Inc; 2014.
Metadata
Title
Update on Pediatric Anti-obesity Medications—Current Landscape and Approach to Prescribing
Authors
Yoon Ji Ahn
Jacqueline Maya
Vibha Singhal
Publication date
30-04-2024
Publisher
Springer US
Published in
Current Obesity Reports
Electronic ISSN: 2162-4968
DOI
https://doi.org/10.1007/s13679-024-00566-z
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Obesity Clinical Trial Summary

At a glance: The STEP trials

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

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