Insulin Glargine 300 U/mL Therapy in Children and Adolescents with Type 1 Diabetes

Abstract

The pharmacokinetic and pharmacodynamic properties of the second-generation basal insulin glargine 300 Units/mL (Gla-300) may be of benefit in the treatment of type 1 diabetes mellitus (T1DM). Gla-300 provides a stable and sustained time-action profile, which is associated with glycaemic control and flexible dosing schedule. This review summarises the available evidence on the safety and efficacy of Gla-300 in children and adolescents with T1DM. Gla-300 is as effective as the first-generation basal insulin glargine 100 Units/mL (Gla-100), a standard of care for patients with diabetes in reducing HbA1c, and shows a lower risk of severe hypoglycaemia and hyperglycaemia in children and adolescents with T1DM. However, Gla-300 and Gla-100 are not bioequivalent and are not directly interchangeable. Real-world studies on patients aged 6-17 years are limited. To date, only one small study assessed the effectiveness and safety of Gla-300 versus Gla-100 in newly diagnosed T1DM paediatric patients, confirming the treatment safety and effectiveness of Gla-300 in clinical practice. Gla-300 is a longer-acting basal insulin alternative in the management of children (aged ≥ 6 years) and adolescents with T1DM.

Fig. 1

Mean INS (A), GIR (B), and blood glucose level (C) after multiple doses in steady state. Figure 1A also shows the LLOQ=5.02 µU·mL⁻¹ threshold. In Figure 1B, the LOESS factor is 0.15. In Figure 1C, which also shows the threshold of blood glucose control (≤ 118 mg·dL⁻¹, the LOESS factor is 0.15. BG blood glucose, GIR glucose infusion rate, INS mean insulin concentration, LLOQ lower limit of quantification, LOESS locally estimated scatterplot smoothing. From [23]

Fig. 2

Mean 24-h glucose profile of the last 2 weeks of each treatment period for the CGM population. A Gla-300 vs Gla-100; B Gla-300/morning injection vs Gla-300/evening injection; C Gla-100/morning injection vs Gla-100/evening injection From [24]

Fig. 3

Glucose infusion rate during the 24-h clamp following a subcutaneous injection of clinical doses of Gla-300 and Gla-100 at t₀ (2000 h). From [27], modified

Fig. 4

Rates of glucose infusion, and PG concentration in the Gla-300 and Deg-100 studies. PG plasma glucose, s.c., subcutaneous. Modified from [35]

Fig. 5

Incidence rate of confirmed and/or severe hypoglycaemic events in reported in the EDITION 4 and EDITION-JP-1 studies. BL baseline, M month, RR rate ratio, W week. Data from [37] and [31]

Fig. 6

Mean HbA1c, LS and FPG variation by visit (A), during the treatment period and during the treatment period (B, C). CI confidence interval, FPG fasting plasma glucose; HbA1c glycated haemoglobin, LS least squares, SE standard error. From [37]

Fig. 7

Cumulative incidence of severe hypoglycaemia events (pooled data). From [43]