Insulin glargine 300 U/ml in type 2 diabetes mellitus patients: results of the EDITION program (review)

Abstract

Unmet medical needs in basal insulin therapy include late initiation of therapy, hypoglycemia, and low patient compliance. Introduction of new basal insulin may cater to these unmet medical needs. New insulin glargine 300 U/mL (Gla-300) (Toujeo) is a long-acting basal insulin with a more even and prolonged PK/PD profile compared to those of insulin glargine 100 (Lantus). The glucose infusion rate profiles and insulin concentration of Gla-300 were more constant and more evenly distributed over 24 h compared to those of glargine 100 U/mL. Stable blood glucose control (≤ 5.5 mmol/L) was maintained approximately 5 h longer with glargine 300 U/mL compared to glargine 100 U/mL. The difference in PK/PD profiles of glargine 300 U/mL and glargine 100 U/mL may be a key to explanation of the Toujeo® clinical features demonstrated in the EDITION program. This review discusses the EDITION clinical program results in type 2 diabetes mellitus (T2MD) patients, except EDITION JP2: on previous basal-bolus therapy (EDITION 1, n=807), previous basal insulin in combination with oral anti-diabetic drug (EDITION 2, n=811), and insulin naive patients (oral anti-diabetic drug excl. SU) (EDITION 3, n=878). The EDITION program was aimed to assess the efficacy and safety of Gla-300 compared to those of glargine 100 U/mL. EDITION programs were multicenter, 1:1 randomized, open-label, parallel group, phase III, and non-inferiority studies, with similar designs and endpoints. The primary endpoint was the non-inferiority of Gla-300 vs glargine 100 U/mL, which was estimated as a HbA1c reduction at 6 months. The main secondary endpoint was the percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L) or severe hypoglycemic events from week 9 to month 6 of treatment. Patients were randomized to glargine 300 U/mL or glargine 100 U/mL once a day, with dose titration seeking fasting plasma glucose of 4.4—5.6 mmol/L. Non-inferiority of glargine 300 U/mL in the HbA1C reduction vs glargine 100 U/mL was confirmed in EDITION 1, EDITION 2, and EDITION 3 studies. According to the results of a pool analysis of these three trials, annualized rates of confirmed (≤3.9 mmol/L) or severe hypoglycemia were lower with glargine 300 U/mL than with glargine 100 U/mL during the night (31% difference in the rate ratio over 6 months, p=0.0002) and at any time (24 h, 14% difference, p=0.0116). Severe hypoglycemia at any time was rare (glargine 300 U/mL: 2.3%; glargine 100 U/mL: 2.6%). Weight gain was low (<1 kg) in both groups, with the gain being less with glargine 300 U/ml [LS mean difference —0.28 kg (95% CI –0.55 to –0.01); p=0.039]. Both treatments were well tolerated, having similar rates of adverse events. In conclusion, glargine 300 U/mL was characterized by the non-inferior efficacy compared to glargine 100 U/mL, a better safety profile (reduced hypoglycemia), and lower weight gain. These advantages may allow for more active insulin dose titration in real clinical practice, contribute to better-sustained glycemic control and patient compliance, and, consequently, improve the prognosis and clinical outcome.