Effect of Single Dose of Insulin Glargine/Lixisenatide Fixed-Ratio Combination (IGlarLixi) on Postprandial Glucodynamic Response in Japanese Patients with Type 2 Diabetes Mellitus

Fixed ratio combination of insulin glargine/lixisenatide (iGlarLixi) is expected to bring benefits such as better efficacy, mitigating barriers to their individual use, and convenient single daily injection. Based on the study results which demonstrated the efficacy and safety of iGlarLixi, approvals from FDA and EMA were obtained. Currently, specific clinical development of iGlarLixi in Japan is ongoing. A randomized, open-label, placebo-controlled, 4-sequence, 4-period, 4-treatment crossover study to investigate the postprandial glucodynamic response to single subcutaneously (SC) dose of iGlarLixi in Japanese T2DM patients was conducted. This study primary aimed at investigating the PD of lixisenatide at doses up to 10 μg in the combination with insulin glargine as compared to placebo and low-dose insulin glargine alone in Japanese T2DM patients. Twenty patients were assigned to one of the four sequences of treatments, all of which included iGlarLixi (5 U/5 μg and 10 U/10 μg), 5 U insulin glargine and placebo. The parameter PPG-AUC_0-2h was evaluated as primary endpoint. The LS mean differences of PPG-AUC_0-2h between iGlarLixi (5 U/5 μg) and placebo, iGlarLixi (10 U/10 μg) and placebo, iGlarLixi (10 U/10 μg) and iGlarLixi (5 U/5 μg), and iGlarLixi (5 U/5 μg) and 5U insulin glargine were -7.48 (p < 0.0001), -10.75 (p < 0.0001), -3.28 (p < 0.0001), and -7.30 (p < 0.0001), respectively. These results demonstrated the 2 doses of iGlarLixi significantly decreased PPG in a dose-dependent manner following a standardized breakfast when compared to placebo. And by combining the complementary therapeutic benefits of insulin glargine predominantly on FPG and the effect of lixisenatide on PPG, the combination product can affect both components of hyperglycemia as a therapeutic principle. No SAEs were reported and no patients discontinued the study. Single SC doses of iGlarLixi were safe and well tolerated.