Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes

Abstract

Aims: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID).

Materials and methods: This randomized, open-label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 μg) for 28 weeks. The primary outcome was the 28-week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments.

Results: A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m2 ; diabetes duration, 8.5 years) received either exenatide QWS-AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean difference, -0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS-AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use.

Conclusions: Exenatide QWS-AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.

Trial registration: ClinicalTrials.gov NCT01652716.

Keywords: autoinjector; exenatide; glucagon-like peptide-1 receptor agonist; type 2 diabetes.

Conflict of interest statement

C. H. W. has received research support and served as a consultant, advisor and speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi. J. R. has received research support from AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hanmi, Intarcia, Janssen, Lexicon, Merck, Novo Nordisk, Pfizer and Sanofi, and has served on advisory boards of, or received consulting honoraria from, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Intarcia, Janssen, Merck, Novo Nordisk and Sanofi. M. L. V. was an employee of Bristol‐Myers Squibb during the conduct of the study. N. I. and P. Ö. are employees of AstraZeneca. F. D. was an employee of AstraZeneca during the development of this manuscript.

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

Figures

Figure 1

Patient disposition. Abbreviations: BID, twice daily; ITT, intention‐to‐treat; QWS‐AI, once‐weekly suspension by autoinjector

Figure 2

A, HbA1c over time (mITT population). B, Probability density function of HbA1c (mITT population). C, FPG over time (mITT population). D, Change in body weight over time (mITT population). E, Plasma glucose during meal test (meal test–evaluable population). F, Plasma exenatide concentration for patients with antibody titers ≤625. Dotted line indicates minimum effective concentration of exenatide for glucose lowering (~50 pg/mL). *P < .05 vs exenatide BID. † P ≤ .01 vs exenatide BID. ‡ P ≤ .001 vs exenatide BID. Abbreviations: BID, twice daily; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; LS, least‐squares; mITT, modified intention‐to‐treat; QWS‐AI, once‐weekly suspension by autoinjector; SD, standard deviation; SE, standard error