Efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) in children and adolescents (6–17 years) with type 1 diabetes: results of the EDITION JUNIOR randomized controlled trial

Abstract

<a><b>Objective</b>: To compare efficacy and safety of insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) in children and adolescents (6–17 years) with type 1 diabetes.</a> <p><b>Study Design:</b> EDITION JUNIOR was a non-inferiority, 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 endpoint was between-group difference in HbA<sub>1c</sub> change from baseline to Week 26. Other assessments included change in fasting plasma glucose (FPG), hypoglycemia, hyperglycemia with ketosis and adverse events. </p> <p><b>Results: </b>In 463 randomized participants (Gla-300, n=233; Gla-100, n=230), comparable least squares (LS) mean (standard error) reductions in HbA<sub>1c</sub> were observed from baseline to Week 26 (−0.40 [0.06] % for both), with LS mean between-group difference of 0.004 % (95% CI: −0.17–0.18), confirming non-inferiority 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, 11.8% with Gla-100. </p> <p><b>Conclusions: </b>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.</p>

Lower risk of severe hypoglycaemia with insulin glargine 300 U/mL versus glargine 100 U/mL in participants with type 1 diabetes: A meta‐analysis of 6‐month phase 3 clinical trials

“…This meta-analysis evaluated pooled data from participants in EDI-TION 4 (NCT01683266), EDITION JP 1 (NCT01689129) and EDI-TION JUNIOR (NCT02735044), which were multicentre, randomized, open-label, parallel-group phase 3 studies involving participants with T1DM, as described previously and in the Supplementary Methods in Appendix S1. [8][9][10][11] All studies had the same primary endpoint: change in HbA1c from baseline to week 26. In EDITION 4 and EDITION JP 1, participants were aged ≥18 years with HbA1c ≥53 to ≥7.0%-≤10% (≤86 mmol/ mol) and had received basal plus prandial insulin for ≥1 year.…”

“…Participants followed a multiple daily injection regimen with basal plus prandial insulin over 26 weeks ( Figure S1 in Appendix S1), titrated to a pre-breakfast self-monitored plasma glucose (SMPG) targets of 4.4 to 7.2 mmol/L (80-130 mg/dL) in EDITION 4 and EDI-TION JP 1 and 5.0 to 7.2 mmol/L (90-130 mg/dL) in EDITION JUNIOR (Table S1 in Appendix S1). [8][9][10] Participants continued their previous prandial insulin regimen, titrated at the investigator's discretion.…”

“…[4][5][6] In clinical trials, Gla-300 and Gla-100 provided comparable glucose reductions, but Gla-300 is associated with lower within-day variability, improved suppression of plasma glucagon and lipid metabolism, and reduced rates of hypoglycaemia, despite greater insulin doses. [5][6][7] The efficacy and safety of Gla-300 versus Gla-100 in participants with type 1 diabetes (T1DM) were investigated in three phase 3, randomized, open-label trials involving international (EDITION 4), 8 Japanese (EDITION JP 1) 9 and paediatric (EDITION JUNIOR) 10 populations. All studies had similar trial designs and demonstrated non-inferiority in glycated haemoglobin (HbA1c) reduction with Gla-300 versus Gla-100, while numerically fewer patients experienced severe hypoglycaemia (SH) with Gla-300 than with Gla-100, during the main 6-month treatment period.…”

“…All studies had similar trial designs and demonstrated non-inferiority in glycated haemoglobin (HbA1c) reduction with Gla-300 versus Gla-100, while numerically fewer patients experienced severe hypoglycaemia (SH) with Gla-300 than with Gla-100, during the main 6-month treatment period. [8][9][10] This post hoc meta-analysis aimed to further explore the risk of SH with initiation of Gla-300 versus Gla-100 in adults, children and adolescents with T1DM, who participated in the three pivotal EDI-TION studies.…”

“…The efficacy and safety of Gla‐300 versus Gla‐100 in participants with type 1 diabetes (T1DM) were investigated in three phase 3, randomized, open‐label trials involving international (EDITION 4), 8 Japanese (EDITION JP 1) 9 and paediatric (EDITION JUNIOR) 10 populations. All studies had similar trial designs and demonstrated non‐inferiority in glycated haemoglobin (HbA1c) reduction with Gla‐300 versus Gla‐100, while numerically fewer patients experienced severe hypoglycaemia (SH) with Gla‐300 than with Gla‐100, during the main 6‐month treatment period 8–10 …”