Impact of baseline glycated haemoglobin, diabetes duration and body mass index on clinical outcomes in the LixiLan-O trial testing a titratable fixed-ratio combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine and lixisenatide monocomponents

Abstract

To determine whether baseline characteristics had an impact on clinical outcomes in the LixiLan-O trial (N = 1170), we compared the efficacy and safety of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U (iGlar) and lixisenatide (Lixi) with iGlar or Lixi alone in patients with uncontrolled type 2 diabetes mellitus (T2DM) on oral therapy. Subgroups according to baseline glycated haemoglobin (HbA1c; <8% or ≥8% [<64 or ≥64 mmol/mol]), T2DM disease duration (<7 or ≥7 years) and body mass index (BMI; <30 or ≥30 kg/m2 ) were investigated. In all subpopulations, iGlarLixi was consistently statistically superior to iGlar and Lixi alone in reducing HbA1c from baseline to week 30; higher proportions of patients achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi vs iGlar and Lixi alone. Compared with iGlar, iGlarLixi resulted in a substantial decrease in 2-hour postprandial plasma glucose levels, and mitigation of weight gain, with no differences among subpopulations in incidence of symptomatic hypoglycaemia. iGlarLixi consistently improved glycaemic control compared with iGlar and Lixi alone, without weight gain or increase in hypoglycaemic risk compared with iGlar in the subpopulations tested, regardless of baseline HbA1c, disease duration and BMI.

Trial registration: ClinicalTrials.gov NCT02058147.

Keywords: GLP-1; glycaemic control; insulin therapy; type 2 diabetes mellitus.

Conflict of interest statement

M. J. D. has acted as consultant, advisory board member and speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi, an advisory board member for Servier and as a speaker for Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc. She has also received grants in support of investigator and investigator‐initiated trials from Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi. L. A. L. has received research funding from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Pfizer and Sanofi, has provided Continuing Medical Education on behalf of AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi, and has acted as an advisor to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier and Takeda. B. G. has acted as an advisory panel/board member for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Medtronic, Merck, Novartis, Novo Nordisk, Roche and Sanofi. He has also acted as a clinical investigator for Abbott, AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Novo Nordisk, Medtronic, Merck, Roche and Sanofi, and received research support from Eli Lilly, Novo Nordisk, Medtronic, Sanofi and Vitalaire.

G. G. has received research support from AstraZeneca, Eli Lilly, Lexicon, Medtronic, Merck, and Novo Nordisk, attended speakers’ bureaus for Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi. F. J. A.‐B. has received honoraria as a speaker and/or consultant from Abbott, AstraZeneca, Bristol‐Myers Squibb, Eli Lilly, GlaxoSmithKline, LifeScan, Madaus, MannKind, Medtronic, Menarini, Merck, Merck Farma y Química, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Schering‐Plough and Solvay. C. Y., W. S., E. N. and E. S. are employees of, and own stock/are shareholders in, Sanofi. J. R. has served on scientific advisory boards and received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Intarcia, Janssen, Lexicon, Novo Nordisk and Sanofi, and has received grants/research support from Asahi, AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hanmi, Intarcia, Janssen, Lexicon, Merck, Novo Nordisk, Sanofi and Pfizer.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Patients who achieved HbA1c target <7% (<53 mmol/mol; responders) by A, baseline HbA1c; B, diabetes duration; and C, BMI.*Treatment comparisons are based on 2‐factor Cochran–Mantel‐Haenszel.