Impact of lixisenatide dose range on clinical outcomes with fixed-ratio combination iGlarLixi in patients with type 2 diabetes

Abstract

Objective: To evaluate the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen (5–20 µg), alone or in fixed-ratio combination with insulin glargine (iGlar; iGlarLixi).

Methods: Data from three clinical studies were analyzed to assess lixisenatide efficacy and safety: a phase 2a trial assessing gastric emptying effects (ACT6011); a phase 2b dose-ranging trial (DRI6012); and a randomized controlled phase 3 trial comparing iGlarLixi with its components of iGlar and lixisenatide (LixiLan-O). Efficacy metrics included glycated hemoglobin A_1c (A1C), post-prandial glucose (PPG) values following a standardized breakfast, fasting plasma glucose (FPG), and weight change. Occurrence of gastrointestinal adverse events was also assessed.

Results: ACT6011: lixisenatide doses from 5–20 μg once daily (QD) suppressed PPG; maximal reductions in mean PPG area under the curve were achieved with doses ≥12.5 µg QD, but doses as low as 5 μg achieved 44% of maximal reduction. DRI6012: lixisenatide doses 5–20 μg QD resulted in significant, dose-dependent decreases in A1C, percentage of patients achieving A1C <7.0%, and 2-h PPG levels; doses of 20 μg achieved complete suppression of PPG. LixiLan-O: iGlarLixi decreased 2-h PPG across the entire dose range. Lixisenatide dose was unrelated to reductions in FPG with iGlarLixi. Similar reductions in A1C were seen with iGlarLixi across all lixisenatide doses.

Conclusions: This analysis demonstrates the clinical benefit of lixisenatide alone or in the formulation of iGlarLixi over the entire dose range of lixisenatide contained in iGlarLixi (5–20 µg), supporting the selection of the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen.

Trial registration: ClinicalTrials.gov identifier: NCT00299871.

Keywords:

• Lixisenatide
• Insulin glargine
• Fixed-ratio combination insulin/GLP-1 receptor agonist
• iGlarLixi

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Declaration of funding

This study was funded by Sanofi US, Inc.

Declaration of financial/other relationships

J.P.F. has served on advisory panels for AstraZeneca and Sanofi, and received research support from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Ionis, Janssen, Johnson & Johnson, Lexicon, Ligand, Merck, Mylan, Novartis AG, Novo Nordisk, Pfizer, Sanofi, Theracos, and vTv Therapeutics. M.L. is an employee of Sanofi-Aventis Deutschland GmbH. W.H. is an employee of Sanofi US, Inc. M.R. is an employee of Sanofi US, Inc. T.D. is an employee and stock/shareholder of Sanofi US, Inc. W.S. is an employee and stock/shareholder of Sanofi-Aventis Deutschland GmbH. N.S. has served on advisory panels for AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen Pharmaceuticals, Lilly, Sanofi, and Teva, has been a speaker for AstraZeneca and Boehringer Ingelheim, and received research support from AstraZeneca and Sanofi.

The authors received writing/editorial support in the preparation of this manuscript by Michael van der Veer, PhD, of Excerpta Medica, funded by Sanofi US, Inc. A CMRO peer reviewer on this manuscript has served as a consultant to Sanofi, as well as several of its competitors. Other CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank Dr John Newton for his input during earlier stages of data interpretation for this publication.