Ezetimibe in the treatment of dyslipidemia in children and adolescents with types 1 and 2 diabetes mellitus: efficacy and safety

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
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Аннотация

Objective: Systematization of the data on the efficacy and safety of ezetimibe in patients aged 6 to 18 years with type 1 (DM1) and type 2 (DM2) diabetes mellitus, and to compare the findings with current clinical guidelines.

Methods: A narrative literature review using the key words «ezetimibe,» «children,» «adolescents,» «diabetes,» «dyslipidemia,» and «low-density lipoprotein» in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov (January 2000 – June 2025) was conducted.

Results: A total of 34 publications were analyzed, including 6 randomized controlled trials (RCTs), 12 observational studies, 5 systematic reviews/meta-analyses, 4 clinical guidelines/consensus papers, 6 reviews and reference articles, and 1 registry document. A single pediatric RCT (n=138, 6–10 years; predominantly heterozygous familial hypercholesterolemia (heFH)) showed a 27% reduction in low-density lipoprotein (LDL) cholesterol with ezetimibe monotherapy, with a safety profile comparable to placebo. In a small crossover study in adolescents with DM1, ezetimibe monotherapy provided a greater reduction in LDL cholesterol compared to simvastatin (≈13 pp); the combination of a statin and ezetimibe was not evaluated in this study. There are no pediatric RCTs in DM2. A network meta-analysis (n=1649; pediatric cohorts with heFH) found that adding ezetimibe to a statin reduced LDL cholesterol by an additional ~16% without increasing the risk of adverse effects. These results are extrapolated to adolescents with diabetes using an individual risk assessment.

Conclusion: Long-term studies of the efficacy and safety of ezetimibe in children with DM2 are required.

Толық мәтін

Рұқсат жабық

Авторлар туралы

Irina Pshenichnikova

Russian Medical Academy of Continuous Professional Education; Z.A. Bashlyaeva Children’s City Clinical Hospital; Research Institute for Healthcare Organization and Medical Management

Хат алмасуға жауапты Автор.
Email: PshenichnikovaII@rmapo.ru
ORCID iD: 0000-0002-0058-3803

Cand. Sci. (Med.), Associate Professor, Speransky Department of Pediatrics, Russian Medical Academy of Continuous Professional Education; Pediatric Cardiologist, Z.A. Bashlyaeva Children’s City Clinical Hospital; Specialist, Research Institute for Healthcare Organization and Medical Management

Ресей, Moscow; Moscow; Moscow

I. Zakharova

Russian Medical Academy of Continuous Professional Education

Email: zakharova-rmapo@yandex.ru
ORCID iD: 0000-0003-4200-4598

Dr. Sci. (Med.), Professor, Head of the Speransky Department of Pediatrics, Honored Doctor of the Russian Federation

Ресей, Moscow

S. Borzakova

Russian Medical Academy of Continuous Professional Education; Z.A. Bashlyaeva Children’s City Clinical Hospital; Research Institute for Healthcare Organization and Medical Management

Email: borzakovasn@zdrav.mos.ru
ORCID iD: 0000-0001-5544-204X

Cand. Sci. (Med.), Associate Professor, Speransky Department of Pediatrics, Russian Medical Academy of Continuous Professional Education; Gastroenterologist, Z.A. Bashlyaeva Children’s City Clinical Hospital; Leading Specialist, Research Institute for Healthcare Organization and Medical Management

Ресей, Moscow; Moscow; Moscow

V. Pupykina

Russian Medical Academy of Continuous Professional Education

Email: vika-pupykina@mail.ru
ORCID iD: 0000-0003-2181-8138

Teaching Assistant, Speransky Department of Pediatrics

Ресей, Moscow

I. Osmanov

Z.A. Bashlyaeva Children’s City Clinical Hospital

Email: OsmanovIM@zdrav.mos.ru
ORCID iD: 0000-0003-3181-9601

Dr. Sci. (Med.), Professor, Chief Physician

Ресей, Moscow

Әдебиет тізімі

  1. Bulut T., Demirel F., Metin A. The prevalence of dyslipidemia and associated factors in children and adolescents with type 1 diabetes. J Pediatr Endocrinol Metab. 2017;30(2):181–7. https://doi.org/10.1515/jpem-2016-0111
  2. Kim G., DeSalvo D., Guffey D., et al. Dyslipidemia in adolescents and young adults with type 1 and type 2 diabetes: a retrospective analysis. Int J Pediatr Endocrinol. 2020;2020:11. https://doi.org/10.1186/s13633-020-00081-7
  3. Paduraru L., Pascalau A.V., Camarasan A., et al. The Impact of Dyslipidemia on the Clinical Profile of Patients With Uncontrolled Diabetes. In Vivo. 2025;39(4):2243–58. https://doi.org/10.21873/invivo.14020
  4. Khoury M., Bigras J.L., Cummings E.A., et al. The Detection, Evaluation, and Management of Dyslipidemia in Children and Adolescents: A Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Clinical Practice Update. Can J Cardiol. 2022;38(8):1168–79. https://doi.org/10.1016/j.cjca.2022.05.002
  5. Bergdahl E., Forsander G., Sundberg F., et al. Investigating the presence and detectability of structural peripheral arterial changes in children with well-regulated type 1 diabetes versus healthy controls using ultra-high frequency ultrasound: a single-centre cross-sectional and case-control study. EClinicalMedicine. 2025;81:103097. https://doi.org/10.1016/j.eclinm.2025.103097
  6. Simeunovic A., Brunborg C., Heier M., et al. Early increase in carotid intima-media thickness in women with childhood-onset type 1 diabetes compared with healthy peers: the Norwegian Atherosclerosis and Childhood Diabetes study. BMJ Open Diab Res Care. 2025;13(1):e004505. https://doi.org/10.1136/bmjdrc-2024-004505.
  7. Järvisalo M.J., Putto-Laurila A., Jartti L., et al. Carotid artery intima-media thickness in children with type 1 diabetes. Diabetes. 2002;51(2):493–8. https://doi.org/10.2337/diabetes.51.2.493
  8. Kartiosuo N., Raitakari O.T., Juonala M., et al. Cardiovascular Risk Factors in Childhood and Adulthood and Cardiovascular Disease in Middle Age. JAMA Netw Open. 2024;7(6):e2418148. https://doi.org/10.1001/jamanetworkopen.2024.18148
  9. American Diabetes Association Professional Practice Committee. 14. Children and Adolescents: Standards of Care in Diabetes-2024. Diab Care. 2024;47(Suppl. 1):S258–81. https://doi.org/10.2337/dc24-S014
  10. Tell S., Nadeau K.J., Eckel R.H. Lipid management for cardiovascular risk reduction in type 1 diabetes. Curr Opin Endocrinol Diab Obes. 2020;27(4):207–14. https://doi.org/10.1097/MED.0000000000000551
  11. American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diab Care. 2024;47(Suppl. 1):S179–218. https://doi.org/10.2337/dc24-S010
  12. Saito I., Azuma K., Kakikawa T., et al. A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia. Lipids Health Dis. 2015;14:40. https://doi.org/10.1186/s12944-015-0036-z
  13. Kusters D.M., Caceres M., Coll M., et al. Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia. J Pediatr. 2015;166(6):1377–84.e1-3. https://doi.org/10.1016/j.jpeds.2015.02.043
  14. Llewellyn A., Simmonds M., Marshall D., et al. Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials. Atherosclerosis. 2025;401:118598. https://doi.org/10.1016/j.atherosclerosis.2024.118598
  15. Singh A., Cho L.S. Nonstatin therapy to reduce low-density lipoprotein cholesterol and improve cardiovascular outcomes. Cleve Clin J Med. 2024;91(1):53–63. https://doi.org/10.3949/ccjm.91a.23058
  16. Sizar O., Nassereddin A., Talati R. Ezetimibe. 2023 Aug 28. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. URL: https://www.ncbi.nlm.nih.gov/books/NBK532879
  17. Araujo M.B., Pacce M.S. A 10-year experience using combined lipid-lowering pharmacotherapy in children and adolescents. J Pediatr Endocrinol Metab. 2016;29(11):1285–91. https://doi.org/10.1515/jpem-2016-0117
  18. Benekos T., Kosmeri C., Vlahos A., Milionis H. Nine-year overview of dyslipidemia management in children with heterozygous familial hypercholesterolemia: a university hospital outpatient lipid clinic project in Northwestern Greece. J Pediatr Endocrinol Metab. 2020;33(4):533–8. https://doi.org/10.1515/jpem-2019-0250
  19. Реестр ОХЛП и ЛВ ЕАЭС. Личный кабинет. [Register of medicinal products and medicinal products of the EAEU. Personal account. (In Russ.)]. URL: https://lk.regmed.ru/Register/EAEU_SmPC
  20. van der Graaf A., Cuffie-Jackson C., Vissers M.N., et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol. 2008;52(17):1421–9. https://doi.org/10.1016/j.jacc.2008.09.002
  21. Wang Y., Zhan S., Du H., et al. Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJ Med. 2022;1(1):e000134. https://doi.org/10.1136/bmjmed-2022-000134
  22. Пшеничникова И.И., Захарова И.Н., Трунина И.Н. и др. Блокатор кишечного всасывания холестерина эзетимиб – перспективное средство коррекции липидного профиля у детей с семейной гиперхолестеринемией. Медицинский совет. 2025;(1):187–94. [Pshenichnikova I.I., Zakharova I.N., Trunina I.N., et al. Ezetimibe, an intestinal cholesterol absorption inhibitor: A promising agent for lipid profile correction in children with familial hypercholesterolemia. Meditsinskiy Sovet. 2025;19(1):187–194. (In Russ)]. https://doi.org/10.21518/ms2025-058
  23. Друк И.В., Нечаева Г.И., Кореннова О.Ю., Ряполова Е.А. Снижение сердечно-сосудистых рисков при сахарном диабете 2 типа: новый класс препаратов – новые перспективы. Лечащий врач. 2015;3:15–21.
  24. Giugliano R.P., Cannon C.P., Blazing M.A., et al; IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2018;137(15):1571–82. https://doi.org/10.1161/CIRCULATIONAHA.117.030950
  25. Ciriacks K., Coly G., Krishnaswami S., et al. Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus. Metab Syndr Relat Disord. 2015;13(2):84–90. https://doi.org/10.1089/met.2014.0114
  26. Semova I., Levenson A.E., Krawczyk J., et al. Type 1 diabetes is associated with an increase in cholesterol absorption markers but a decrease in cholesterol synthesis markers in a young adult population. J Clin Lipidol. 2019;13(6):940–6. https://doi.org/10.1016/j.jacl.2019.09.008
  27. Bishop F.K., Wadwa R.P., Ellis S., et al. Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes. Int J Pediatr Endocrinol. 2012;2012(1):24. https://doi.org/10.1186/1687-9856-2012-24
  28. Nakamura A., Sato K., Kanazawa M., et al. Impact of decreased insulin resistance by ezetimibe on postprandial lipid profiles and endothelial functions in obese, non-diabetic-metabolic syndrome patients with coronary artery disease. Heart Vessels. 2019;34(6):916–25. https://doi.org/10.1007/s00380-018-1319-x
  29. Wu H., Shang H., Wu J. Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials. Endocrine. 2018;60(2):229–39. https://doi.org/10.1007/s12020-018-1541-4
  30. Toth P., Catapano A., Farnier M., et al. Ezetimibe does not increase fasting glucose levels more than statins alone in non-diabetic, hypercholesterolemic patients. JACC. 2015;241(1):e216. https://doi.org/10.1016/S0735-1097(15)61633-3
  31. Sridharan K., Sivaramakrishnan G. Ezetimibe-associated rhabdomyolysis: A comprehensive assessment of the USFDA adverse event reporting system using disproportionality analysis, case reviews, and meta-analysis of randomized clinical trials. J Clin Lipidol. 2025;19(2):327–36. https://doi.org/10.1016/j.jacl.2024.12.010
  32. Klement M., Drexel H., Saely C.H. Impact of ezetimibe on markers of inflammation in patients treated with statins: a systematic review. Inflammopharmacol. 2023;31(4):1647–56. https://doi.org/10.1007/s10787-023-01209-w
  33. Shah A.S., Barrientos-Pérez M., Chang N., et al. ISPAD Clinical Practice Consensus Guidelines 2024: Type 2 Diabetes in Children and Adolescents. Horm Res Paediatr. 2024;97(6):555–83. https://doi.org/10.1159/000543033
  34. Yoon J.M. Dyslipidemia in children and adolescents: when and how to diagnose and treat? Pediatr Gastroenterol Hepatol Nutr. 2014;17(2):85–92. https://doi.org/10.5223/pghn.2014.17.2.85

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