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Published in: Diabetology & Metabolic Syndrome 1/2024

Open Access 01-12-2024 | Type 2 Diabetes | Research

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis

Authors: Louise Buonalumi Tacito Yugar, Luis Gustavo Sedenho-Prado, Isadora Maria Castilho da Silva Ferreira, Cleide Aparecida Moreira Silva, Andrei C. Sposito, Cintia Cercato

Published in: Diabetology & Metabolic Syndrome | Issue 1/2024

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Abstract

Background

Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus.

Methods

Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects.

Results

Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low.

Conclusions

Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.

Trial registration

PROSPERO identifier: CRD42023393020.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wu H, Patterson CC, Zhang X, Ghani RBA, Magliano DJ, Boyko EJ, et al. Worldwide estimates of incidence of type 2 diabetes in children and adolescents in 2021. Diabetes Res Clin Pract. 2022;185:109785.CrossRefPubMed Wu H, Patterson CC, Zhang X, Ghani RBA, Magliano DJ, Boyko EJ, et al. Worldwide estimates of incidence of type 2 diabetes in children and adolescents in 2021. Diabetes Res Clin Pract. 2022;185:109785.CrossRefPubMed
2.
go back to reference Lawrence JM, Divers J, Isom S, Saydah S, Imperatore G, Pihoker C, et al. Trends in Prevalence of Type 1 and type 2 diabetes in children and adolescents in the US, 2001–2017. JAMA. 2021;326(8):717–27.CrossRefPubMedPubMedCentral Lawrence JM, Divers J, Isom S, Saydah S, Imperatore G, Pihoker C, et al. Trends in Prevalence of Type 1 and type 2 diabetes in children and adolescents in the US, 2001–2017. JAMA. 2021;326(8):717–27.CrossRefPubMedPubMedCentral
3.
go back to reference Shah AS, Zeitler PS, Wong J, Pena AS, Wicklow B, Arslanian S, et al. ISPAD Clinical Practice Consensus guidelines 2022: type 2 diabetes in children and adolescents. Pediatr Diabetes. 2022;23(7):872–902.CrossRefPubMed Shah AS, Zeitler PS, Wong J, Pena AS, Wicklow B, Arslanian S, et al. ISPAD Clinical Practice Consensus guidelines 2022: type 2 diabetes in children and adolescents. Pediatr Diabetes. 2022;23(7):872–902.CrossRefPubMed
4.
go back to reference Dabelea D, Stafford JM, Mayer-Davis EJ, D’Agostino R Jr., Dolan L, Imperatore G, et al. Association of Type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA. 2017;317(8):825–35.CrossRefPubMedPubMedCentral Dabelea D, Stafford JM, Mayer-Davis EJ, D’Agostino R Jr., Dolan L, Imperatore G, et al. Association of Type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA. 2017;317(8):825–35.CrossRefPubMedPubMedCentral
5.
go back to reference Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, et al. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med. 2019;381(7):637–46.CrossRefPubMed Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, et al. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med. 2019;381(7):637–46.CrossRefPubMed
6.
go back to reference Tamborlane WV, Bishai R, Geller D, Shehadeh N, Al-Abdulrazzaq D, Vazquez EM, et al. Once-weekly Exenatide in Youth with type 2 diabetes. Diabetes Care. 2022;45(8):1833–40.CrossRefPubMedPubMedCentral Tamborlane WV, Bishai R, Geller D, Shehadeh N, Al-Abdulrazzaq D, Vazquez EM, et al. Once-weekly Exenatide in Youth with type 2 diabetes. Diabetes Care. 2022;45(8):1833–40.CrossRefPubMedPubMedCentral
7.
go back to reference Ryan PM, Patterson E, Kent RM, Stack H, O’Connor PM, Murphy K et al. Recombinant incretin-secreting microbe improves metabolic dysfunction in High-Fat Diet Fed rodents. Sci Rep. 2017;7(1). Ryan PM, Patterson E, Kent RM, Stack H, O’Connor PM, Murphy K et al. Recombinant incretin-secreting microbe improves metabolic dysfunction in High-Fat Diet Fed rodents. Sci Rep. 2017;7(1).
8.
go back to reference McLean BA, Wong CK, Campbell JE, Hodson DJ, Trapp S, Drucker DJ. Revisiting the complexity of GLP-1 action from sites of synthesis to receptor activation. Endocr Rev. 2021;42(2):101–32.CrossRefPubMed McLean BA, Wong CK, Campbell JE, Hodson DJ, Trapp S, Drucker DJ. Revisiting the complexity of GLP-1 action from sites of synthesis to receptor activation. Endocr Rev. 2021;42(2):101–32.CrossRefPubMed
9.
go back to reference American Diabetes Association Professional Practice C. 14. Children and Adolescents: Standards of Care in Diabetes—2024. Diabetes Care. 2023;47(Supplement_1):S258-S81. American Diabetes Association Professional Practice C. 14. Children and Adolescents: Standards of Care in Diabetes—2024. Diabetes Care. 2023;47(Supplement_1):S258-S81.
10.
go back to reference Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRefPubMed Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRefPubMed
11.
go back to reference Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013Available from guidelinedevelopment.org/handbook. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013Available from guidelinedevelopment.org/handbook.
12.
go back to reference GRADEpro GDT. GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime; 2023. Available from gradepro.org. GRADEpro GDT. GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime; 2023. Available from gradepro.org.
13.
go back to reference Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Reviews. 2021;10(1):89.CrossRef Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Reviews. 2021;10(1):89.CrossRef
14.
go back to reference Klein DJ, Battelino T, Chatterjee DJ, Jacobsen LV, Hale PM, Arslanian S. Liraglutide’s safety, tolerability, pharmacokinetics, and pharmacodynamics in pediatric type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Technol Ther. 2014;16(10):679–87.CrossRefPubMedPubMedCentral Klein DJ, Battelino T, Chatterjee DJ, Jacobsen LV, Hale PM, Arslanian S. Liraglutide’s safety, tolerability, pharmacokinetics, and pharmacodynamics in pediatric type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Technol Ther. 2014;16(10):679–87.CrossRefPubMedPubMedCentral
15.
go back to reference Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19(4):524–36.CrossRefPubMed Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19(4):524–36.CrossRefPubMed
16.
go back to reference Potts JE, Gray LJ, Brady EM, Khunti K, Davies MJ, Bodicoat DH. The Effect of Glucagon-Like peptide 1 receptor agonists on weight loss in type 2 diabetes: a systematic review and mixed treatment comparison Meta-analysis. PLoS ONE. 2015;10(6):e0126769.CrossRefPubMedPubMedCentral Potts JE, Gray LJ, Brady EM, Khunti K, Davies MJ, Bodicoat DH. The Effect of Glucagon-Like peptide 1 receptor agonists on weight loss in type 2 diabetes: a systematic review and mixed treatment comparison Meta-analysis. PLoS ONE. 2015;10(6):e0126769.CrossRefPubMedPubMedCentral
17.
go back to reference Sun F, Wu S, Guo S, Yu K, Yang Z, Li L, et al. Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetes Res Clin Pract. 2015;110(1):26–37.CrossRefPubMed Sun F, Wu S, Guo S, Yu K, Yang Z, Li L, et al. Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetes Res Clin Pract. 2015;110(1):26–37.CrossRefPubMed
18.
go back to reference Sharma AK, Metzger DL, Rodd CJ. Prevalence and severity of high blood pressure among children based on the 2017 American Academy of Pediatrics Guidelines. JAMA Pediatr. 2018;172(6):557–65.CrossRefPubMedPubMedCentral Sharma AK, Metzger DL, Rodd CJ. Prevalence and severity of high blood pressure among children based on the 2017 American Academy of Pediatrics Guidelines. JAMA Pediatr. 2018;172(6):557–65.CrossRefPubMedPubMedCentral
19.
go back to reference Song P, Zhang Y, Yu J, Zha M, Zhu Y, Rahimi K, et al. Global prevalence of hypertension in children: a systematic review and Meta-analysis. JAMA Pediatr. 2019;173(12):1154–63.CrossRefPubMedPubMedCentral Song P, Zhang Y, Yu J, Zha M, Zhu Y, Rahimi K, et al. Global prevalence of hypertension in children: a systematic review and Meta-analysis. JAMA Pediatr. 2019;173(12):1154–63.CrossRefPubMedPubMedCentral
20.
go back to reference Chadda KR, Cheng TS, Ong KK. GLP-1 agonists for obesity and type 2 diabetes in children: systematic review and meta-analysis. Obes Rev. 2021;22(6):e13177.CrossRefPubMed Chadda KR, Cheng TS, Ong KK. GLP-1 agonists for obesity and type 2 diabetes in children: systematic review and meta-analysis. Obes Rev. 2021;22(6):e13177.CrossRefPubMed
21.
go back to reference Ryan PM, Seltzer S, Hayward NE, Rodriguez DA, Sless RT, Hawkes CP. Safety and Efficacy of Glucagon-Like Peptide-1 receptor agonists in children and adolescents with obesity: a Meta-analysis. J Pediatr. 2021;236:137 – 47.e13. Ryan PM, Seltzer S, Hayward NE, Rodriguez DA, Sless RT, Hawkes CP. Safety and Efficacy of Glucagon-Like Peptide-1 receptor agonists in children and adolescents with obesity: a Meta-analysis. J Pediatr. 2021;236:137 – 47.e13.
22.
23.
go back to reference Wang SY, Andrews CA, Herman WH, Gardner TW, Stein JD. Incidence and risk factors for developing Diabetic Retinopathy among youths with type 1 or type 2 diabetes throughout the United States. Ophthalmology. 2017;124(4):424–30.CrossRefPubMed Wang SY, Andrews CA, Herman WH, Gardner TW, Stein JD. Incidence and risk factors for developing Diabetic Retinopathy among youths with type 1 or type 2 diabetes throughout the United States. Ophthalmology. 2017;124(4):424–30.CrossRefPubMed
24.
go back to reference Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE. Young-onset type 2 diabetes mellitus — implications for morbidity and mortality. Nat Reviews Endocrinol. 2020;16(6):321–31.CrossRef Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE. Young-onset type 2 diabetes mellitus — implications for morbidity and mortality. Nat Reviews Endocrinol. 2020;16(6):321–31.CrossRef
25.
go back to reference Badaru A, Klingensmith GJ, Dabelea D, Mayer-Davis EJ, Dolan L, Lawrence JM, et al. Correlates of treatment patterns among youth with type 2 diabetes. Diabetes Care. 2014;37(1):64–72.CrossRefPubMed Badaru A, Klingensmith GJ, Dabelea D, Mayer-Davis EJ, Dolan L, Lawrence JM, et al. Correlates of treatment patterns among youth with type 2 diabetes. Diabetes Care. 2014;37(1):64–72.CrossRefPubMed
26.
go back to reference Effects of Treatment of Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes With. Metformin alone or in combination with insulin glargine on β-Cell function: comparison of responses in youth and adults. Diabetes. 2019;68(8):1670–80.PubMedPubMedCentral Effects of Treatment of Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes With. Metformin alone or in combination with insulin glargine on β-Cell function: comparison of responses in youth and adults. Diabetes. 2019;68(8):1670–80.PubMedPubMedCentral
27.
go back to reference Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes: developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). Eur Heart J. 2023;44(39):4043–140.CrossRefPubMed Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes: developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). Eur Heart J. 2023;44(39):4043–140.CrossRefPubMed
28.
go back to reference Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral Semaglutide and Cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841–51.CrossRefPubMed Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral Semaglutide and Cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841–51.CrossRefPubMed
29.
go back to reference Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, et al. Effects of once-weekly Exenatide on Cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228–39.CrossRefPubMedPubMedCentral Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, et al. Effects of once-weekly Exenatide on Cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228–39.CrossRefPubMedPubMedCentral
32.
go back to reference Linyun F, Juliana Chizo A, Nivedita A, Chirag B, Evelien G. Glucose monitoring and glucose lowering agents for children and young people with type 2 diabetes: summary of updated NICE guidance. BMJ. 2023;382:p1686. Linyun F, Juliana Chizo A, Nivedita A, Chirag B, Evelien G. Glucose monitoring and glucose lowering agents for children and young people with type 2 diabetes: summary of updated NICE guidance. BMJ. 2023;382:p1686.
33.
go back to reference Telo GH, Cureau FV, Szklo M, Bloch KV, Schaan BD. Prevalence of type 2 diabetes among adolescents in Brazil: findings from Study of Cardiovascular Risk in adolescents (ERICA). Pediatr Diabetes. 2019;20(4):389–96.CrossRefPubMed Telo GH, Cureau FV, Szklo M, Bloch KV, Schaan BD. Prevalence of type 2 diabetes among adolescents in Brazil: findings from Study of Cardiovascular Risk in adolescents (ERICA). Pediatr Diabetes. 2019;20(4):389–96.CrossRefPubMed
Metadata
Title
The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis
Authors
Louise Buonalumi Tacito Yugar
Luis Gustavo Sedenho-Prado
Isadora Maria Castilho da Silva Ferreira
Cleide Aparecida Moreira Silva
Andrei C. Sposito
Cintia Cercato
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2024
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-024-01337-5

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