Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan-L trial

Abstract

Aims: To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose-lowering drugs.

Materials and methods: In this exploratory analysis of LixiLan-L (N = 736), efficacy outcomes were assessed within population subgroups derived from the following baseline characteristics: glycated haemoglobin [HbA1c; <8%, ≥8% (<64, ≥64 mmol/mol)]; duration of T2DM (<10, ≥10 years); body mass index (<30, ≥30 kg/m2 ). Furthermore, the incidence of symptomatic hypoglycaemia with plasma glucose ≤3.9 mmol/L (≤70 mg/dL) was also analysed according to the same subgroups.

Results: Compared with the iGlar treatment group, patients treated with iGlarLixi showed consistently greater reductions in HbA1c during the treatment period, with higher percentages of patients achieving the HbA1c target level of <7% (<53 mmol/mol) in all of the subpopulations tested (P < .0001 for all), having consistent mitigation of body weight gain and with no major differences in the incidence of hypoglycaemia.

Conclusions: iGlarLixi consistently improved glycaemic control compared with iGlar in all baseline characteristic subgroups of patients with T2DM inadequately controlled with insulin, including difficult-to-treat subgroups of patients with long duration of diabetes, obesity and high HbA1c. Clinical trial number: NCT02058160 (clinicaltrials.gov).

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

Conflict of interest statement

C. W. has served on advisory boards for AstraZeneca, Janssen and Sanofi; as a consultant for AstraZeneca, Janssen and Sanofi; and received research support from AstraZeneca and Novo Nordisk; participated in speakers’ bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi. R. C. B. has served on advisory panels for Amgen, Eli Lilly and Sanofi; participated in speakers’ bureau for AstraZeneca, Bristol‐Myers Squibb, Eli Lilly, Merck and Sanofi. V. R. A. has served as a consultant for Adocia, Janssen, Novo Nordisk and Sanofi, and is an employee of MedStar Health Research Institute, which has received research support from Amylin, AstraZeneca, Bristol‐Myers Squibb, Boehringer Ingelheim, Eisai, GI Dynamics, GlaxoSmithKline, Halozyme, Hanmi, Intarcia, Janssen, Novo Nordisk, Sanofi and Takeda. M. P. D. has served on advisory panels for Sanofi and Lilly; participated in speakers’ bureau for Sanofi, Lilly, Novo Nordisk, AstraZeneca, Janssen and MSD. C. K. has received research support from Adocia, AstraZeneca, Biocon, Boehringer Ingelheim, Dance Biopharm, Gulf Pharmaceutical Industries, Johnson & Johnson, Eli Lilly, Marvel LifeSciences, Medtronic, Medimmune, Novo Nordisk, Novartis, Roche Diagnostics, Sanofi, Senseonics and Zealand Pharma; and has received advisory, speaker and travel grants from Sanofi. W. S., C. Y., E. N. and E. S. are employees of, and own stock/shareholders in, Sanofi. R. M. B. has served on a scientific advisory board, consulted or performed clinical research with Abbott Diabetes Care, Bayer, Becton Dickinson, Boehringer Ingelheim, AstraZeneca, DexCom, Eli Lilly, Halozyme, Hygieia, Johnson & Johnson, Medtronic, Merck, Novo Nordisk, Roche, Sanofi and Takeda. R. M. B.’s employer, the non‐profit HealthPartners Institute, contracts for his services and no personal income goes to Dr Bergenstal. He has inherited Merck stock.

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

Figures

Figure 1

Percentages of patients who achieved HbA1c target <7% (<53 mmol/mol) for baseline A, HbA1c; B, diabetes duration and C, BMI subpopulations. *Treatment comparisons within subgroups are based on 2‐factor Cochran–Mantel–Haenszel. An adjustment was made for the treatment differences based on the randomization strata. BMI, body mass index; HbA1c, glycated haemoglobin; T2DM, type 2 diabetes mellitus

Figure 2

Mean weight change for baseline A, HbA1c; B, diabetes duration and C, BMI subpopulations. *Treatment comparisons within subgroups are based on 2‐factor Cochran–Mantel–Haenszel. BMI, body mass index; HbA1c, glycated haemoglobin; T2DM, type 2 diabetes mellitus

Figure 3

Hypoglycaemia incidence for baseline A, HbA1c; B, diabetes duration and C, BMI subpopulations. *Weighted average of proportion difference between treatment groups. Treatment comparisons are based on 2‐factor Cochran–Mantel–Haenszel. An adjustment was made for the treatment differences based on the randomization strata. Hypoglycaemia defined as plasma glucose ≤3.9 mmol/L (≤70 mg/dL). BMI, body mass index; e/p‐y, events per patient year; HbA1c, glycated haemoglobin; T2DM, type 2 diabetes mellitus