Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial

Abstract

In this post hoc analysis of the randomized controlled LixiLan-O trial in insulin-naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed-ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs.

Trial registration: ClinicalTrials.gov NCT02058147.

Keywords: glycaemic control; iGlarLixi; insulin glargine 100 U; lixisenatide; type 2 diabetes mellitus.

Conflict of interest statement

M. J. D. serves on Advisory Panels for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novo Nordisk, Sanofi‐Aventis and Servier; serves as a consultant to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novo Nordisk and Sanofi‐Aventis; has received research support (grants in support of investigator trials) from Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi‐Aventis; and is a member of speakers bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi‐Aventis and Takeda.

D. R‐J. serves on Advisory Panels for, is a Board member of and consultant to, and has received research support from AstraZeneca, Eli Lilly, Novo Nordisk and Sanofi; and is a member of speakers bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi and Takeda.

T. M. B. serves on Advisory Panels for AstraZeneca, Boehringer Ingelheim, Napp Pharmaceuticals, Novo Nordisk and Sanofi; and has received research support from AstraZeneca, Bayer and Shire.

F. J. L‐G. serves on Advisory Panels for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi; is a Board member of AstraZeneca, Boehringer Ingelheim, Janssen, Novo Nordisk and Sanofi; and is a member of speakers bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novo Nordisk and Sanofi.

G. R. G. serves on Advisory Panels for AbbVie, AstraZeneca, Merck Sharp & Dohme, Novo Nordisk, Pfizer and Sanofi; and is a member of speakers bureaus for Amgen, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, LifeScan, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier and Takeda.

D. Z. has nothing to disclose.

M. B. is an employee of and stock/shareholder in Sanofi; is Honorary Associate Professor at the University of Swansea; and is Non‐Executive Director of Ashford and St Peter's Hospital NHS Foundation Trust.

C. D‐B. is an employee of and stock/shareholder in Sanofi.

R. J. M. serves on Advisory Panels for Eli Lilly, Novo Nordisk, Sanofi; and is a member of speakers bureaus for Eli Lilly and Sanofi.

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

Figures

Figure 1

HbA1c and body weight outcomes for patients with T2DM from the overall LixiLan‐O study population,12 for patients with baseline HbA1c ≥9% and for patients with two OADs according to randomization strata at screening (mITT population). Error bars indicate SE. ANCOVA, analysis of covariance; BL, baseline; CI, confidence interval; HbA1c, glycated haemoglobin; iGlar, insulin glargine 100 U; iGlarLixi, insulin glargine and lixisenatide; Lixi, lixisenatide; LOCF, last observation carried forward; LS, least squares; mITT, modified intent‐to‐treat; MMRM, mixed‐effect model with repeated measures; OAD, oral antihyperglycaemic drug; SD, standard deviation; SE, standard error; T2DM, type 2 diabetes mellitus. aOverall LixiLan‐O data based on MMRM analysis. bLS mean difference for iGlarLixi vs iGlar or lixisenatide alone, ANCOVA; LOCF was used to handle missing data. cDifferences in proportion of patients achieving HbA1c <7% were analysed based on weighted average differences between treatment groups from each strata using a Cochran‐Mantel‐Haenszel method