Low incidence of gastrointestinal adverse events over time with a fixed-ratio combination of insulin glargine and lixisenatide versus lixisenatide alone

Abstract

This post hoc analysis of gastrointestinal (GI) adverse events (AEs) from the phase 3 LixiLan-L (NCT02058160) and LixiLan-O (NCT02058147) trials aimed to determine the frequency and timing of nausea, vomiting, and diarrhoea for iGlarLixi, a titratable, fixed-ratio combination of insulin glargine 100 units/mL (iGlar) and lixisenatide, versus iGlar alone or iGlar and lixisenatide alone, in patients with type 2 diabetes uncontrolled with oral antidiabetes drugs (OADs) or basal insulin ± OADs. In iGlarLixi-treated patients, the rate of GI AEs during the initial weeks of treatment was lower versus patients treated with lixisenatide alone (9.6% and 11.7% of iGlarLixi-treated patients in LixiLan-L and LixiLan-O, respectively, vs. 27.5% of lixisenatide-treated patients in LixiLan-O). Beyond day 60, these rates were generally low and similar to those of lixisenatide. These lower rates are likely due to the gradual titration of lixisenatide in iGlarLixi. Median durations of intermittent GI AEs in the iGlarLixi arms were 6.0, 2.0 and 2.5 days (LixiLan-L), and 5.0, 1.0 and 3.5 days (LixiLan-O), respectively. iGlarLixi-associated GI AEs were transient, mostly mild or moderate in severity, and occurred mainly during initial titration.

Keywords: fixed-ratio combination; gastrointestinal adverse events; insulin glargine; lixisenatide.

Conflict of interest statement

Author contributions

J. M. T., M. R., T. D., J. W. and J. L. co‐developed the concept of the study, interpreted the data, critically reviewed the manuscript drafts, and provided final approval of the version of the manuscript to be submitted. J. C. collected the data, performed the analyses and provided the data tables, interpreted the data, critically reviewed the manuscript drafts, and provided final approval of the version of the manuscript to be submitted. J. M. T. is the guarantor of this work and, as such, had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Incidence of nausea and vomiting per week with iGlarLixi A, versus iGlar in Lixilan‐L and B, versus lixisenatide in Lixilan‐O. Each subject could contribute with multiple events over time, but only the first event was counted each week

Figure 2

Severity of nausea, vomiting and diarrhoea with iGlarLixi in A, LixiLan‐L and B, LixiLan‐O. AE, adverse event; GI, gastrointestinal. The pie charts show the percentage of patients with/without a GI AE; the bars show the percentage of events (i.e. one patient can contribute with multiple events)