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Efficacy and safety of liraglutide for weight management in children and adolescents: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Obesity represents a risk factor for multiple coexisting conditions and complications. Liraglutide is mainly reserved for populations who fail to achieve weight loss goals with lifestyle changes alone. This study aims to systematically evaluate the safety and effectiveness of liraglutide in weight management in children and youth. A systematic search was performed of PubMed, Embase, Cochrane Library, and Web of Science from inception to February 23rd, 2023. Randomized controlled trials (RCTs) evaluating the effects of liraglutide in children and youth were included. All data analyses were performed using Review Manager 5.3 version. Seven eligible articles were finally included, covering a population of 547 participants. Liraglutide use was associated with reduced body weight (WMD: -2.13 kg; 95%CI: -4.23, -0.03), BMI (WMD: -1.56 kg/m2; 95% CI: -2.41, -0.7), and BMI SDS (WMD: -0.17; 95% CI: -0.26, -0.08). Similar associations were found in HbA1c (WMD: -0.29%; 95% CI: -0.52, -0.06) and fasting plasma glucose (SMD: -0.39; 95% CI: -0.64, -0.14). Subgroup analysis shows an improvement in HbA1c control only among children with type 2 diabetes (WMD: -1.06%; 95% CI: -1.44, -0.67). No differences were found in fasting serum insulin, SBP, DBP, HDL, LDL, and TG between liraglutide and placebo. In addition, no difference was found in the frequencies of adverse events, serious adverse events, and adverse events resulting in discontinuation of therapy between liraglutide and placebo treatment groups.

Conclusion: Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents.

What is Known:

• A few first-line treatment of these children and adolescents with overweight and obesity is a multi-component lifestyle intervention.

• Lifestyle modifications are not suitable for all individuals, therefore, new treatment strategies urgent need to be established.

What is New:

• This is the first meta-analysis conducted to assess the efficacy and safety of liraglutide for weight management in children and adolescents.

• Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents.

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Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Jebeile H, Kelly AS, O’Malley G, Baur LA (2022) Obesity in children and adolescents: epidemiology, causes, assessment, and management. Lancet Diabetes Endocrinol 10:351–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Collaboration NCDRF (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390:2627–2642

    Article  Google Scholar 

  3. Simmonds M, Llewellyn A, Owen CG, Woolacott N (2016) Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev 17:95–107

    Article  CAS  PubMed  Google Scholar 

  4. The NS, Suchindran C, North KE, Popkin BM, Gordon-Larsen P (2010) Association of adolescent obesity with risk of severe obesity in adulthood. JAMA 304:2042–2047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Horesh A, Tsur AM, Bardugo A, Twig G (2021) Adolescent and childhood obesity and excess morbidity and mortality in young adulthood—a systematic review. Curr Obes Rep 10:301–310

    Article  PubMed  Google Scholar 

  6. Jebeile H, Cardel MI, Kyle TK, Jastreboff AM (2021) Addressing psychosocial health in the treatment and care of adolescents with obesity. Obesity (Silver Spring) 29:1413–1422

    Article  PubMed  Google Scholar 

  7. Cardel MI, Atkinson MA, Taveras EM, Holm JC, Kelly AS (2020) Obesity treatment among adolescents: a review of current evidence and future directions. JAMA Pediatr 174:609–617

    Article  PubMed  PubMed Central  Google Scholar 

  8. Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, Yanovski JA (2017) Pediatric obesity—assessment, treatment, and prevention: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 102:709–757

    Article  PubMed  PubMed Central  Google Scholar 

  9. Nicolucci A, Maffeis C (2022) The adolescent with obesity: what perspectives for treatment? Ital J Pediatr 48:9

    Article  PubMed  PubMed Central  Google Scholar 

  10. van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH (2014) Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond) 38:784–793

    Article  PubMed  Google Scholar 

  11. McLean BA, Wong CK, Campbell JE, Hodson DJ, Trapp S, Drucker DJ (2021) Revisiting the complexity of GLP-1 action from sites of synthesis to receptor activation. Endocr Rev 42:101–132

    Article  PubMed  Google Scholar 

  12. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135

    Article  PubMed  PubMed Central  Google Scholar 

  14. Luo D, Wan X, Liu J, Tong T (2018) Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 27:1785–1805

    Article  PubMed  Google Scholar 

  15. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods G, Cochrane Statistical Methods G (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928

    Article  PubMed  PubMed Central  Google Scholar 

  16. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  17. van der Heijden LB, Feskens EJ, Janse AJ (2014) Maintenance interventions for overweight or obese children and adolescents who participated in a treatment program: study protocol for a systematic review. Syst Rev 3:111

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhou QX, Wang ZY, Zhao HF, Wang S (2017) The effects of GLP-1 analogues on pre-diabetes of the children. Exp Ther Med 13:1426–1430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mastrandrea LD, Witten L, Carlsson Petri KC, Hale PM, Hedman HK, Riesenberg RA (2019) Liraglutide effects in a paediatric (7–11 y) population with obesity: a randomized, double-blind, placebo-controlled, short-term trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics. Pediatr Obes 14:e12495

    Article  PubMed  PubMed Central  Google Scholar 

  20. Diene G, Angulo M, Hale PM, Jepsen CH, Hofman PL, Hokken-Koelega A, Ramesh C, Turan S, Tauber M (2022) Liraglutide for weight management in children and adolescents with Prader-Willi syndrome and obesity. J Clin Endocrinol Metab 108:4–12

    Article  PubMed  PubMed Central  Google Scholar 

  21. Danne T, Biester T, Kapitzke K, Jacobsen SH, Jacobsen LV, Petri KCC, Hale PM, Kordonouri O (2017) Liraglutide in an adolescent population with obesity: a randomized, double-blind, placebo-controlled 5-week trial to assess safety, tolerability, and pharmacokinetics of liraglutide in adolescents aged 12–17 years. J Pediatr 181:146-153.e143

    Article  CAS  PubMed  Google Scholar 

  22. Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, Jalaludin MY, Kovarenko M, Libman I, Lynch JL, Rao P, Shehadeh N, Turan S, Weghuber D, Barrett T (2019) Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med 381:637–646

    Article  CAS  PubMed  Google Scholar 

  23. Klein DJ, Battelino T, Chatterjee DJ, Jacobsen LV, Hale PM, Arslanian S, De Schepper J, Barrett T, Bone M, Randel T, Blumer J, Christensen M, Ferry R, Hazan L, Klein DJ, Lopez X, Neufeld N, Toltzis P, Tsalikian E, Wadwa RP, Wintergerst K (2014) Liraglutide’s safety, tolerability, pharmacokinetics, and pharmacodynamics in pediatric type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Technol Ther 16:679–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S (2020) A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med 382:2117–2128

    Article  CAS  PubMed  Google Scholar 

  25. Moon S, Lee J, Chung HS, Kim YJ, Yu JM, Yu SH, Oh CM (2021) Efficacy and safety of the new appetite suppressant, liraglutide: a meta-analysis of randomized controlled trials. Endocrinol Metab (Seoul) 36:647–660

    Article  CAS  PubMed  Google Scholar 

  26. Farpour-Lambert NJ, Baker JL, Hassapidou M, Holm JC, Nowicka P, O’Malley G, Weiss R (2015) Childhood obesity is a chronic disease demanding specific health care–a position statement from the Childhood Obesity Task Force (COTF) of the European Association for the Study of Obesity (EASO). Obes Facts 8:342–349

    Article  PubMed  PubMed Central  Google Scholar 

  27. Collaborators GBDO, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A et al (2017) Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 377:13–27

    Article  Google Scholar 

  28. Jastreboff AM, Kotz CM, Kahan S, Kelly AS, Heymsfield SB (2019) Obesity as a disease: the obesity society 2018 position statement. Obesity (Silver Spring) 27:7–9

    Article  PubMed  Google Scholar 

  29. Bray GA, Kim KK, Wilding JPH, World Obesity Federation (2017) Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev 18:715–723

    Article  CAS  PubMed  Google Scholar 

  30. Salam RA, Padhani ZA, Das JK, Shaikh AY, Hoodbhoy Z, Jeelani SM, Lassi ZS, Bhutta ZA (2020) Effects of lifestyle modification interventions to prevent and manage child and adolescent obesity: a systematic review and meta-analysis. Nutrients 12

  31. Janicke DM, Mitchell TB, Basch MC, Ding K, Jones LC, Pinto S, Moorman EL, Reynolds CM, Gonzalez-Louis RC, Wolock ER (2021) Meta-analysis of lifestyle modification interventions addressing overweight and obesity in preschool-age children. Health Psychol 40:631–641

    Article  PubMed  Google Scholar 

  32. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ (2012) Prader-Willi syndrome. Genet Med 14:10–26

    Article  CAS  PubMed  Google Scholar 

  33. Brambilla P, Crino A, Bedogni G, Bosio L, Cappa M, Corrias A, Delvecchio M, Di Candia S, Gargantini L, Grechi E, Iughetti L, Mussa A, Ragusa L, Sacco M, Salvatoni A, Chiumello G, Grugni G, Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology (2011) Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity. Nutr Metab Cardiovasc Dis 21:269–276

    CAS  PubMed  Google Scholar 

  34. Crino A, Fintini D, Bocchini S, Grugni G (2018) Obesity management in Prader-Willi syndrome: current perspectives. Diabetes Metab Syndr Obes 11:579–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nadeau KJ, Anderson BJ, Berg EG, Chiang JL, Chou H, Copeland KC, Hannon TS, Huang TT, Lynch JL, Powell J, Sellers E, Tamborlane WV, Zeitler P (2016) Youth-onset type 2 diabetes consensus report: current status, challenges, and priorities. Diabetes Care 39:1635–1642

    Article  PubMed  PubMed Central  Google Scholar 

  36. Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P (2018) Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association. Diabetes Care 41:2648–2668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zeitler P, Arslanian S, Fu J, Pinhas-Hamiel O, Reinehr T, Tandon N, Urakami T, Wong J, Maahs DM (2018) ISPAD clinical practice consensus guidelines 2018: type 2 diabetes mellitus in youth. Pediatr Diabetes 19(Suppl 27):28–46

    Article  PubMed  Google Scholar 

  38. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB (2018) Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 41:2669–2701

    Article  PubMed  PubMed Central  Google Scholar 

  39. Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, Yanovski JA (2017) Response to Letter: “Pediatric obesity—assessment, treatment, and prevention: an endocrine society clinical practice guideline.” J Clin Endocrinol Metab 102:2123–2124

    Article  PubMed  PubMed Central  Google Scholar 

  40. Reinehr T, Lass N, Toschke C, Rothermel J, Lanzinger S, Holl RW (2016) Which amount of BMI-SDS reduction is necessary to improve cardiovascular risk factors in overweight children? J Clin Endocrinol Metab 101:3171–3179

    Article  CAS  PubMed  Google Scholar 

  41. Ells LJ, Rees K, Brown T, Mead E, Al-Khudairy L, Azevedo L, McGeechan GJ, Baur L, Loveman E, Clements H, Rayco-Solon P, Farpour-Lambert N, Demaio A (2018) Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews. Int J Obes (Lond) 42:1823–1833

    Article  PubMed  Google Scholar 

  42. Tirosh A, Shai I, Afek A, Dubnov-Raz G, Ayalon N, Gordon B, Derazne E, Tzur D, Shamis A, Vinker S, Rudich A (2011) Adolescent BMI trajectory and risk of diabetes versus coronary disease. N Engl J Med 364:1315–1325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Marcus C, Danielsson P, Hagman E (2022) Pediatric obesity-Long-term consequences and effect of weight loss. J Intern Med 292:870–891

    Article  PubMed  PubMed Central  Google Scholar 

  44. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705

    Article  CAS  PubMed  Google Scholar 

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HG and JJG wrote the main manuscript and fully participated in all analyses. YMZ and HG contributed to the study concept and design. JJG participated in literature search, data extraction, and quality assessment. All authors read and approved the final manuscript.

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Correspondence to Junjun Guo.

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Gou, H., Zhai, Y. & Guo, J. Efficacy and safety of liraglutide for weight management in children and adolescents: a systematic review and meta-analysis of randomized controlled trials. Eur J Pediatr 182, 5095–5108 (2023). https://doi.org/10.1007/s00431-023-05186-8

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