Efficacy and Safety of Insulin Glargine 300 Units/mL (Gla-300) Versus Insulin Glargine 100 Units/mL (Gla-100) in Children and Adolescents (6-17 years) With Type 1 Diabetes: Results of the EDITION JUNIOR Randomized Controlled Trial

Thomas Danne, William V Tamborlane, Oleg A Malievsky, Denise R Franco, Tomoyuki Kawamura, Marek Demissie, Elisabeth Niemoeller, Harmonie Goyeau, Marek Wardecki, Tadej Battelino, Thomas Danne, William V Tamborlane, Oleg A Malievsky, Denise R Franco, Tomoyuki Kawamura, Marek Demissie, Elisabeth Niemoeller, Harmonie Goyeau, Marek Wardecki, Tadej Battelino

Abstract

Objective: To compare efficacy and safety of insulin glargine 300 units/mL (Gla-300) and 100 units/mL (Gla-100) in children and adolescents (6-17 years old) with type 1 diabetes.

Research design and methods: EDITION JUNIOR was a noninferiority, international, open-label, two-arm, parallel-group, phase 3b trial. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to achieve fasting self-monitored plasma glucose levels of 90-130 mg/dL (5.0-7.2 mmol/L), with continuation of prior prandial insulin. The primary end point was change in HbA1c from baseline to week 26. Other assessments included change in fasting plasma glucose (FPG), hypoglycemia, hyperglycemia with ketosis, and adverse events.

Results: In 463 randomized participants (Gla-300, n = 233; Gla-100, n = 230), comparable least squares (LS) mean (SE) reductions in HbA1c were observed from baseline to week 26 (-0.40% [0.06%] for both groups), with LS mean between-group difference of 0.004% (95% CI -0.17 to 0.18), confirming noninferiority at the prespecified 0.3% (3.3 mmol/mol) margin. Mean FPG change from baseline to week 26 was also similar between groups. During the 6-month treatment period, incidence and event rates of severe or documented (≤70 mg/dL [≤3.9 mmol/L]) hypoglycemia were similar between groups. Incidence of severe hypoglycemia was 6.0% with Gla-300 and 8.8% with Gla-100 (relative risk 0.68 [95% CI 0.35-1.30]). Incidence of any hyperglycemia with ketosis was 6.4% with Gla-300 and 11.8% with Gla-100.

Conclusions: Gla-300 provided similar glycemic control and safety profiles to Gla-100 in children and adolescents with type 1 diabetes, indicating that Gla-300 is a suitable therapeutic option in this population.

Trial registration: ClinicalTrials.gov NCT02735044.

© 2020 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Glycemic control. Mean (SE) HbA1c by visit (A) and LS mean change (B) during the 26-week randomized period. C: FPG by visit during the 26-week randomized period (ITT population).

References

    1. Nathan DM, Genuth S, Lachin J, et al. .; Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986
    1. Nathan DM, Bayless M, Cleary P, et al. .; DCCT/EDIC Research Group . Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study at 30 years: advances and contributions. Diabetes 2013;62:3976–3986
    1. Barnea-Goraly N, Raman M, Mazaika P, et al. .; Diabetes Research in Children Network (DirecNet) . Alterations in white matter structure in young children with type 1 diabetes. Diabetes Care 2014;37:332–340
    1. Mauras N, Mazaika P, Buckingham B, et al. .; Diabetes Research in Children Network (DirecNet) . Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes 2015;64:1770–1779
    1. Abraham MB, Jones TW, Naranjo D, et al. . ISPAD Clinical Practice Consensus Guidelines 2018: assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr Diabetes 2018;19(Suppl. 27):178–192
    1. Tsalikian E, Tamborlane W, Xing D, et al. .; Diabetes Research in Children Network (DirecNet) Study Group . Blunted counterregulatory hormone responses to hypoglycemia in young children and adolescents with well-controlled type 1 diabetes. Diabetes Care 2009;32:1954–1959
    1. Hershey T, Perantie DC, Warren SL, Zimmerman EC, Sadler M, White NH. Frequency and timing of severe hypoglycemia affects spatial memory in children with type 1 diabetes. Diabetes Care 2005;28:2372–2377
    1. Gagnum V, Stene LC, Jenssen TG, et al. . Causes of death in childhood-onset type 1 diabetes: long-term follow-up. Diabet Med 2017;34:56–63
    1. Frier BM. How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev 2008;24:87–92
    1. Highlights of prescribing information : LANTUS (insulin glargine injection) for subcutaneous injection [Internet]. Available from . Accessed 7 March 2019
    1. Lantus summary of product characteristics [Internet] . Accessed 7 March 2019.
    1. Ashwell SG, Gebbie J, Home PD. Twice-daily compared with once-daily insulin glargine in people with type 1 diabetes using meal-time insulin aspart. Diabet Med 2006;23:879–886
    1. Becker RHA, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. New insulin glargine 300 units·mL−1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units·mL−1. Diabetes Care 2015;38:637–643
    1. Steinstraesser A, Schmidt R, Bergmann K, Dahmen R, Becker RHA. Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml. Diabetes Obes Metab 2014;16:873–876
    1. Yki-Järvinen H, Bergenstal R, Ziemen M, et al. .; EDITION 2 Study Investigators . New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care 2014;37:3235–3243
    1. Riddle MC, Bolli GB, Ziemen M, Muehlen-Bartmer I, Bizet F, Home PD; EDITION 1 Study Investigators . New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care 2014;37:2755–2762
    1. Bolli GB, Riddle MC, Bergenstal RM, et al. .; on behalf of the EDITION 3 study investigators . New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3). Diabetes Obes Metab 2015;17:386–394
    1. Home PD, Bergenstal RM, Bolli GB, et al. . New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 1 diabetes: a randomized, phase 3a, open-label clinical trial (EDITION 4). Diabetes Care 2015;38:2217–2225
    1. Matsuhisa M, Koyama M, Cheng X, et al. .; EDITION JP 1 Study Group . New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese adults with type 1 diabetes using basal and mealtime insulin: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 1). Diabetes Obes Metab 2016;18:375–383
    1. Terauchi Y, Koyama M, Cheng X, et al. . New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2). Diabetes Obes Metab 2016;18:366–374
    1. Bergenstal RM, Bailey TS, Rodbard D, et al. . Comparison of insulin glargine 300 units/mL and 100 units/mL in adults with type 1 diabetes: continuous glucose monitoring profiles and variability using morning or evening injections. Diabetes Care 2017;40:554–560
    1. American Diabetes Association 13. Children and adolescents: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019;42(Suppl. 1):S148–S164
    1. International Hypoglycaemia Study Group Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017;40:155–157
    1. Workgroup on Hypoglycemia, American Diabetes Association Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245–1249
    1. IDF/ISPAD global guideline for diabetes in childhood and adolescence [Internet], 2011 Available from . Accessed 10 April 2019.
    1. Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus [Internet], 2012 London, U.K., European Medicines Agency. Available from . Accessed 19 November 2019.
    1. Guidance for Industry. Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention [Internet], 2008 Available from . Accessed 19 November 2019.
    1. DiMeglio LA, Acerini CL, Codner E, et al. . ISPAD Clinical Practice Consensus Guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes 2018;19(Suppl. 27):105–114
    1. Foster NC, Beck RW, Miller KM, et al. . State of type 1 diabetes management and outcomes from the T1D Exchange in 2016-2018. Diabetes Technol Ther 2019;21:66–72
    1. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet 2014;383:69–82
    1. Markowitz JT, Garvey KC, Laffel LM. Developmental changes in the roles of patients and families in type 1 diabetes management. Curr Diabetes Rev 2015;11:231–238
    1. Dündar BN, Dündar N, Eren E. Comparison of the efficacy and safety of insulin glargine and insulin detemir with NPH insulin in children and adolescents with type 1 diabetes mellitus receiving intensive insulin therapy. J Clin Res Pediatr Endocrinol 2009;1:181–187
    1. Urakami T, Mine Y, Aoki M, Okuno M, Suzuki J. A randomized crossover study of the efficacy and safety of switching from insulin glargine to insulin degludec in children with type 1 diabetes. Endocr J 2017;64:133–140
    1. Hopkinson HE, Jacques RM, Gardner KJ, Amiel SA, Mansell P. Twice- rather than once-daily basal insulin is associated with better glycaemic control in type 1 diabetes mellitus 12 months after skills-based structured education in insulin self-management. Diabet Med 2015;32:1071–1076
    1. Youssef D, El Abbassi A, Woodby G, Peiris AN. Benefits of twice-daily injection with insulin glargine: a case report and review of the literature. Tenn Med 2010;103:42–43
    1. Owens DR. Pharmacokinetics and pharmacodynamics of insulin glargine 300 U/mL in the treatment of diabetes and their clinical relevance. Expert Opin Drug Metab Toxicol 2016;12:977–987
    1. Toujeo 300 units/ml SoloStar, solution for injection in a pre-filled pen [Internet] Berskshire, U.K., Sanofi. Available from . Accessed 27 November 2019.
    1. Thalange N, Deeb L, Iotova V, et al. . Insulin degludec in combination with bolus insulin aspart is safe and effective in children and adolescents with type 1 diabetes. Pediatr Diabetes 2015;16:164–176

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj