Efficacy and safety of lixisenatide in a predominantly Asian population with type 2 diabetes insufficiently controlled with basal insulin: The GetGoal-L-C randomized trial

Abstract

Aims: To assess the effects on glycaemic control of lixisenatide vs placebo as add-on treatment to basal insulin (BI) ± metformin and effects on glycated haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2 diabetes (T2D).

Methods: Patients (n = 448) with inadequately controlled T2D were randomized (1:1) to lixisenatide or placebo as add-on to BI ± metformin for 24 weeks after an 8-week run-in phase, during which BI was titrated to a target self-monitored plasma glucose (SMPG; 4.4-5.6 mmol/L). The primary endpoint was absolute change in HbA1c from baseline to week 24. Secondary efficacy endpoints included: percentage of responders; changes in 2-hour postprandial plasma glucose (PPG); 7-point SMPG (daily average); body weight (BW); total daily BI dose; fasting plasma glucose; and safety assessments.

Results: Baseline demographics were similar in the two treatment groups. After insulin optimization during run-in, lixisenatide was superior to placebo in mean change from baseline (7.9% [standard deviation {s.d.}, 0.66] and 7.9% [0.70], respectively) to week 24 in HbA1c (least squares mean [standard error {s.e.}] change -0.62% [0.09] vs -0.11% [0.09]; P < .0001, respectively) and higher proportions of patients achieved HbA1c targets. Two-hour PPG, daily mean SMPG and mean BW were reduced further and daily BI dose was lower with lixisenatide than placebo (-1.12 kg vs 0.04 kg [P < .0001]; -3.0 U vs -1.9 U [P = .0033], respectively). Treatment-emergent adverse events were greater with lixisenatide than placebo (63.8% vs 40.8%, respectively). The incidence of symptomatic hypoglycaemia was similar (lixisenatide 15.6% vs placebo 13.5%).

Conclusions: In Asian patients insufficiently controlled on BI ± metformin, lixisenatide was superior to placebo in glycaemic control, with a tolerability profile in line with other glucagon-like peptide-1 receptor agonists.

Clinical trial number: NCT01632163 (clinicaltrials.gov).

Keywords: GLP-1; incretin therapy; incretins; randomized trial.

Conflict of interest statement

W. Y. attended the advisory board of Novo Nordisk, received investigator‐initiated trial research funds from AstraZeneca, has been a speaker for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme China, Novo Nordisk, Sanofi Aventis and Servier, and has received honoraria and travel support as the advisory board member from Merck & Co., Inc, outside the submitted work.

K. M., Z. Z., L. L., X. X., D. Z., A. V. R. have no conflict of interest to declare. L. S. M. was an investigator for AstraZeneca, Boehringer Ingelheim, Novartis, Novo Nordisk and Sanofi. N. X. Z., I. L., E. N., S. S. are employees of Sanofi.

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

Figures

Figure 1

Study design

Figure 2

A, Mean ± s.e. HbA1c (%) and B, mean HbA1c response rate by visit to week 24 LOCF (mITT population). Measurements obtained up to 14 days after the last injection of lixisenatide/placebo are included