Glycemic control metrics during exercise in children with type 1 diabetes treated with domestic insulin aspart biosimilars using a hybrid closed-loop system

Introduction. Achieving and maintaining target glycemic levels in children and adolescents with type 1 diabetes (T1D) remains a challenging task, especially during physical activity, which significantly increases the risk of acute complications. This study evaluated metabolic control parameters in children and adolescents engaged in regular sports activities and receiving therapy with domestic biosimilars of insulin aspart under the conditions of a hybrid closed-loop (HCL) systems.

Aim. To evaluate the efficacy and safety of domestic insulin aspart biosimilars in HCL systems in physically active children with T1D.

Materials and methods. A retrospective comparative study was conducted involving 36 children and adolescents with T1D treated using HCL systems and regularly engaged in sports. Study participants received therapy with the insulin aspart biosimilars RinFastNic (n = 17) and RinFast (n = 19). The observation period was 12 weeks. Key glycemic control metrics (TIR, TAR, TBR, CV, HbA1c) were assessed based on continuous glucose monitoring data.

Results. The RinFastNic group demonstrated statistically superior metabolic control metrics compared to the RinFast group: Time in Range (TIR) was 81.41% vs. 67.74% (p < 0.05), Time Above Range (TAR) – 13.18% vs. 28.53% (p < 0.05). Hypoglycemia metrics (TBR) were comparable. Сoefficient of variation (33.01% vs. 38.46%, p < 0.05) and HbA1c level (6.4% vs. 6.8%, p < 0.05) were also better in the main group.

Conclusions. The use of the insulin aspart biosimilar RinFastNic in HCL systems is associated with a significant improvement in glycemic control in physically active children with T1D, primarily due to increased TIR and reduced hyperglycemia, without an increased risk of hypoglycemia. The results indicate the importance of considering the pharmacokinetic properties of insulin for optimizing HCL system performance under conditions of physical activity.

1. ElSayed NA, McCoy RG, Aleppo G, Beverly EA, Briggs Early K, Bruemm D et al. 14. Children and Adolescents: Standards of Care in Diabetes–2025. Diabetes Care. 2025;48(Suppl. 1):S283–S305. https://doi.org/10.2337/dc25-S014.

2. de Bock M, Codner E, Craig ME, Huynh T, Maahs DM, Mahmud FH et al. ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes. Pediatr Diabetes. 2022;23(8):1270–1276. https://doi.org/10.1111/pedi.13455.

3. Riddell MC, Gallen IW, Smart CE, Taplin CE, Adolfsson P, Lumb AN et al. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol. 2017;5(5):377–390. https://doi.org/10.1016/S2213-8587(17)30014-1.

4. Rothacker KM, Armstrong S, Smith GJ, Benjanuvatra N, Lay B, Adolfsson P et al. Acute hyperglycaemia does not have a consistent adverse effect on exercise performance in recreationally active young people with type 1 diabetes: a randomised crossover in-clinic study. Diabetologia. 2021;64(8):1737–1748. https://doi.org/10.1007/s00125-021-05465-9.

5. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC et al. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019;381(18):1707–1717. https://doi.org/10.1056/NEJMoa1907863.

6. Messer LH, Berget C, Forlenza GP. A Clinical Guide to Advanced Diabetes Devices and Closed-Loop Systems Using the CARES Paradigm. Diabetes Technol Ther. 2019;21(8):462–469. https://doi.org/10.1089/dia.2019.0105.

7. Foulds A, Josey C, Kehlenbrink S, Rollman BL, Chang CH, Lalama C et al. Human versus Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings (HumAn-1): protocol for a randomised controlled trial. BMJ Open. 2025;15(1):e092432. https://doi.org/10.1136/bmjopen-2024-092432.

8. Urakami T. The Advanced Diabetes Technologies for Reduction of the Frequency of Hypoglycemia and Minimizing the Occurrence of Severe Hypoglycemia in Children and Adolescents with Type 1 Diabetes. J Clin Med. 2023;12(3):781. https://doi.org/10.3390/jcm12030781.

9. Beato-Víbora PI, Gallego-Gamero F, Lázaro-Martín L, Romero-Pérez MDM, Arroyo-Díez FJ. Prospective Analysis of the Impact of Commercialized Hybrid Closed-Loop System on Glycemic Control, Glycemic Variability, and Patient-Related Outcomes in Children and Adults: A Focus on Superiority Over Predictive Low-Glucose Suspend Technology. Diabetes Technol Ther. 2020;22(12):912–919. https://doi.org/10.1089/dia.2019.0400.

10. Heinemann L, Davies M, Home P, Forst T, Vilsbøll T, Schnell O. Understanding Biosimilar Insulins – Development, Manufacturing, and Clinical Trials. J Diabetes Sci Technol. 2023;17(6):1649–1661. https://doi.org/10.1177/19322968221105864.

11. Heise T, DeVries JH. Biosimilar insulins: Narrative review of the regulatory frame-work and registration studies. Diabetes Obes Metab. 2025;27(Suppl. 5):16–23. https://doi.org/10.1111/dom.16320.

12. Abitbol A, Chu L. What do the guidelines say about use of biosimilar insulin therapy? Simple practical considerations to guide clinicians in different patient subgroups – Sharing Canadian perspectives. Diabetes Obes Metab. 2025;27(Suppl. 5):36–44. https://doi.org/10.1111/dom.16278.

13. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E et al. A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes. N Engl J Med. 2020;383(9):836–845. https://doi.org/10.1056/NEJMoa2004736.

14. Lachal S, Tourki Y, Franc S, Huneker E, Charpentier G, Benhamou PY. Hybrid Closed-Loop Control with Ultrarapid Lispro Compared with Standard Insulin Aspart and Faster Insulin Aspart: An In Silico Study. J Diabetes Sci Technol. 2023;17(1):176–185. https://doi.org/10.1177/19322968211046021.

15. Diaz C JL, Colmegna P, Breton MD. Maximizing Glycemic Benefits of Using Faster Insulin Formulations in Type 1 Diabetes: In Silico Analysis Under Open- and Closed-Loop Conditions. Diabetes Technol Ther. 2023;25(4):219–230. https://doi.org/10.1089/dia.2022.0468.

16. Tagougui S, Taleb N, Legault L, Suppère C, Messier V, Boukabous I et al. A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies. Diabetologia. 2020;63(11):2282–2291. https://doi.org/10.1007/s00125-020-05244-y.

17. Dutta D, Mohindra R, Mahajan K, Sharma M. Performance of Fast-Acting Aspart Insulin as Compared to Aspart Insulin in Insulin Pump for Managing Type 1 Diabetes Mellitus: A Meta-Analysis. Diabetes Metab J. 2023;47(1):72–81. https://doi.org/10.4093/dmj.2022.0035.

18. Boughton CK, Hartnell S, Thabit H, Poettler T, Herzig D, Wilinska ME et al. Hybrid closed-loop glucose control with faster insulin aspart compared with standard insulin aspart in adults with type 1 diabetes: A double-blind, multicentre, multinational, randomized, crossover study. Diabetes Obes Metab. 2021;23(6):1389–1396. https://doi.org/10.1111/dom.14355.

19. Oktavian P, Kencono Wungu CD, Mudjanarko SW, Amin IM. A comparison of ultra-rapid and rapid insulin in automated insulin delivery for type 1 diabetes: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2025;27(5):2658–2669. https://doi.org/10.1111/dom.16268.

20. Petruzelkova L, Neuman V, Plachy L, Kozak M, Obermannova B, Kolouskova S et al. First Use of Open-Source Automated Insulin Delivery AndroidAPS in Full Closed-Loop Scenario: Pancreas4ALL Randomized Pilot Study. Diabetes Technol Ther. 2023;25(5):315–323. https://doi.org/10.1089/dia.2022.0562.

21. Wilkinson T, Tomic D, Boyle E, Burren D, Elghattis Y, Jenkins A et al. Study protocol for a randomised open-label clinical trial examining the safety and efficacy of the Android Artificial Pancreas System (AAPS) with advanced bolus-free features in adults with type 1 diabetes: the ‘CLOSE IT’ (Closed Loop Open SourcE In Type 1 diabetes) trial. BMJ Open. 2024;14(2):e078171. https://doi.org/10.1136/bmjopen-2023-078171.

22. Lei M, Lin B, Ling P, Liu Z, Yang D, Deng H et al. Efficacy and safety of Android artificial pancreas system use at home among adults with type 1 diabetes mellitus in China: protocol of a 26-week, free-living, randomised, open-label, two-arm, two-phase, crossover trial. BMJ Open. 2023;13(8):e073263. https://doi.org/10.1136/bmjopen-2023-073263.

23. Yamada T, Kamata R, Ishinohachi K, Shojima N, Ananiadou S, Nom H et al. Biosimilar vs originator insulins: Systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(7):1787–1792. https://doi.org/10.1111/dom.13291.

24. Ismail S, Abu Esba L, Khan M, Al-Abdulkarim H, Modimagh H, Yousef C. An Institutional Guide for Formulary Decisions of Biosimilars. Hosp Pharm. 2023;58(1):38–48. https://doi.org/10.1177/00185787221138007.

25. Bas TG. Innovative Formulation Strategies for Biosimilars: Trends Focused on Buffer-Free Systems, Safety, Regulatory Alignment, and Intellectual Property Challenges. Pharmaceuticals. 2025;18(6):908. https://doi.org/10.3390/ph18060908.

26. Saverskaya EN, Eltysheva TE, Karpov DS, Korobkina MP, Zaikin PG. Biosimilars of aspart and lispro analogues in the insulin pump. RMJ. 2022;(1):9–14. (In Russ.) Available at: https://www.rmj.ru/articles/endokrinologiya/Primenenie_biosimilyarov_insulinovyh_analogov_aspart_ilizpro_vpompe/.