iGlarLixi, a titratable once-daily fixed-ratio combination of basal insulin and lixisenatide for intensifying type 2 diabetes management for patients inadequately controlled on basal insulin with or without oral agents

Abstract

Background: Achieving and maintaining glycemic control is important for people with type 2 diabetes (T2D), to reduce disease-related complications and mortality; however, about half of US patients fail to meet glycemic targets. iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide for once-daily administration, was recently approved by the US Food and Drug Administration for use in adults with T2D inadequately controlled on basal insulin (<60 U daily) or lixisenatide. iGlar and lixisenatide have complementary mechanisms of action, primarily targeting fasting plasma glucose and postprandial plasma glucose, respectively. In the US, iGlarLixi is available in a 3:1 ratio of iGlar and lixisenatide, respectively, across the dosage range of 15–60 U of iGlar and 5–20 µg of lixisenatide.

Methods: This study identified phase 3 trials which assessed the efficacy and safety of iGlarLixi. Relevant trials were LixiLan-O, which compared iGlarLixi with iGlar or lixisenatide alone in insulin-naïve patients, and LixiLan-L, which compared iGlarLixi with iGlar alone in insulin-experienced patients.

Results: Patients on iGlarLixi experienced greater A1C reduction and were more likely to achieve A1C <7.0% than its comparators. iGlarLixi mitigated the weight gain associated with iGlar without increasing hypoglycemia risk, and resulted in a lower frequency of gastrointestinal adverse events compared with lixisenatide.

Conclusions: iGlarLixi provides a new approach to therapy intensification in patients with T2D. iGlarLixi showed greater A1C efficacy compared with either iGlar or lixisenatide, mitigating iGlar-associated weight gain, without increasing hypoglycemia risk, and reducing the gastrointestinal side-effects seen with lixisenatide.

Keywords:

• Fixed-ratio combination
• iGlarLixi
• GLP-1 receptor agonist
• type 2 diabetes

Transparency

Declaration of funding

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Declaration of financial/other relationships

N.S. has disclosed that he has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Sanofi, and Teva, and has acted as a speaker for AstraZeneca and Boehringer Ingelheim. R.D. has no potential conflict of interest to disclose. E.J. has disclosed that he has served on an advisory board for Novo Nordisk and Sanofi, received grant/research from Lexicon Pharmaceutical, and has been a member of a speakers bureau for Medtronic and Novo Nordisk. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing/editorial assistance was provided by Catarina Fernandes, PhD of Excerpta Medica and was funded by Sanofi US, Inc.