Rates of hypoglycaemia are lower in patients treated with insulin degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of the hypoglycaemia definition used

Abstract

Aims: To re-analyse, using a series of alternative hypoglycaemia definitions, the data from 2 trials, DUAL I and V, in which the once-daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) was compared with basal insulin therapy.

Material and methods: Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and according to whether treatments were administered in the morning or afternoon. Rates of hypoglycaemia for the definitions of confirmed and American Diabetes Association (ADA)-documented symptomatic hypoglycaemia were compared according to age, gender and body mass index (BMI).

Results: Although hypoglycaemia rates differed according to the alternative hypoglycaemia definitions, rates were consistently lower with IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin concentrations being lower with IDegLira at end of treatment, confirmed and nocturnal-confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar U100, irrespective of dosing time. The definitions of confirmed and ADA-documented symptomatic hypoglycaemia did not have a significant effect on the treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when further assessed by baseline age, gender and BMI.

Conclusions: Treatment with IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia regardless of dosing time and definition of hypoglycaemia used. The choice of hypoglycaemia definition did not influence the results of analyses when stratified by age, sex and BMI.

Keywords: IDegLira; hypoglycaemia; hypoglycaemia rates; insulin degludec; insulin glargine U100; liraglutide.

Conflict of interest statement

P. N. has received research funding from Novo Nordisk and works with Eli Lilly, Sanofi, Astra Zeneca and other companies. R. C. has appeared on speakers’ bureau or advisory boards for Novo Nordisk, Merck Sharp & Dohme, AstraZeneca, Eli Lilly & Co, Boehringer Ingelheim, Amgen and Sanofi Aventis. E. J. has received research support from Novo Nordisk, Novartis, Gilead, Roche, Miltenyi Biotech, Biotest, Wacker Chemie, Fresnius DFG, BMBF, EU, JDRF, VW‐Stiftung and has appeared on speakers' bureau or advisory boards for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, MSD, Janssen, Roche and Novartis. UT Southwestern (on behalf of I. L.) received research funding and/or consulting fees from NovoNordisk, Novartis, GIDynamics, Merck and Pfizer. I.L. received non‐financial support from Novo Nordisk, Sanofi, AstraZeneca and Boehringer Ingelheim. S. H. has served on scientific advisory boards and provided consultancy for which his institution has received remuneration from Eli Lilly & Co, Novo Nordisk, Takeda, Merck Sharp & Dohme and Becton Dickinson. S. H. has also served as a speaker for which he received remuneration from AstraZeneca, Eli Lilly & Co, Novo Nordisk, Boehringer Ingelheim and Takeda and has received research support from Medtronic UK Ltd. H. J. is an employee and shareholder of Novo Nordisk. L. L. is an employee and shareholder of Novo Nordisk.

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

Figures

Figure 1

Estimated rate ratio of hypoglycaemia by hypoglycaemia definition for A, IDegLira vs IDeg and B, IDegLira vs liraglutide for DUAL I ext and C, IDegLira vs IGlar U100 for DUAL V. Data based on the full analysis set. The number of hypoglycaemic events was analysed using a negative binomial regression model with a log link and the logarithm of the time period in which a hypoglycaemic episode was considered treatment‐emergent as offset. The model included treatment, country/region and relevant stratification factors (in DUAL I ext only) of previous OAD treatment, baseline HbA1c stratum, and substudy participation as fixed effects. CI, confidence interval; OAD, oral antidiabetic drug

Figure 2

Cumulative mean number of ADA‐documented symptomatic hypoglycaemic episodes per patient for A, IDegLira, IDeg and liraglutide for DUAL I and DUAL I ext and (B) IDegLira and IGlar U100 in DUAL V. Data based on the safety analysis set. ADA‐documented symptomatic hypoglycaemic episode defined as typical symptoms of hypoglycaemia confirmed by a plasma glucose ≤3.9 mmol/L (≤70 mg/dL)

Figure 3

Estimated rate ratio of hypoglycaemia (based on original definition) by dosing time for A, IDegLira vs IDeg and B, IDegLira vs liraglutide for DUAL I and DUAL I ext and C, IDegLira vs IGlar U100 for DUAL V. Data based on the full analysis set. The number of hypoglycaemic events was analysed using a negative binomial regression model with a log link and the logarithm of the time period in which a hypoglycaemic episode was considered treatment‐emergent as offset. The model included treatment, country/region and relevant stratification factors (in DUAL I/ext only) of previous OAD treatment, baseline HbA1c stratum, and substudy participation as fixed effects. CI, confidence interval; OAD, oral antidiabetic drug