Effect of a single dose of insulin glargine/lixisenatide fixed ratio combination (iGlarLixi) on postprandial glucodynamic response in Japanese patients with type 2 diabetes mellitus: A phase I randomized trial

Megumi Inoue, Martin Lorenz, Hideya Muto, Roland Wesch, Yasuhiro Hashimoto, Megumi Inoue, Martin Lorenz, Hideya Muto, Roland Wesch, Yasuhiro Hashimoto

Abstract

This report describes novel clinical data assessing the pharmacodynamics of insulin glargine/lixisenatide (iGlarLixi) compared with placebo and insulin glargine alone, to determine pharmacokinetics of lixisenatide, and to assess safety of iGlarLixi in Japanese people with type 2 diabetes mellitus (T2DM). In a single-centre, open-label, randomized, placebo-controlled cross-over study, participants received subcutaneous iGlarLixi 5 U/5 μg and 10 U/10 μg, placebo, and 5 U insulin glargine. The primary endpoint was area under the postprandial plasma glucose (PPG) curve (AUC0-2h ). A total of 20 participants completed all study periods. iGlarLixi 5 U/5 μg and 10 U/10 μg reduced mean PPG dose-dependently compared with placebo and insulin glargine 5 U. Both combinations significantly reduced PPG-AUC0-2h dose-dependently compared with placebo (least squares mean difference -7.48 mmol h/L for 5 U/5 μg, -10.75 mmol h/L for 10 U/10 μg; P < 0.0001). iGlarLixi 5 U/5 μg reduced PPG-AUC0-2h significantly compared with insulin glargine 5 U (-0.76 mmol h/L; P < 0.0001). No symptomatic hypoglycaemia occurred during the study. iGlarLixi single subcutaneous injections significantly and dose-dependently reduced PPG compared to placebo or insulin glargine in Japanese participants with T2DM. iGlarLixi was safe and well tolerated, and would be expected to provide the 24-hour plasma glucose-lowering effects of insulin glargine and the postprandial antihyperglycaemic effects of lixisenatide.

Keywords: GLP-1 analogue; basal insulin; glycaemic control; pharmacodynamics; pharmacokinetics; phase I-II study.

Conflict of interest statement

M.I. reports no conflict of interest. M.L. and R.W. are employed by Sanofi‐Aventis Germany GmbH. H.M. and Y. H. are employed by Sanofi K.K. Japan.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Pharmacodynamic results of insulin glargine/lixisenatide fixed ratio combination treatment: changes in serum and plasma glucose levels over time. †Time is shown in reference to the start of breakfast (0 hour on the x‐axis). Breakfast was served 1 hour after administration of the study drug

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