Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

Abstract

Introduction: Investigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.

Research design and methods: In this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.

Results: In total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28-52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of -1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of -1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.

Conclusions: Switching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.

Trial registration number: NCT01652716.

Keywords: Glucagon-Like Peptide-1 (GLP-1); glycemic control; type 2 diabetes.

Conflict of interest statement

Competing interests: CHW is an advisor, speaker, and consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi, an advisor for Abbott, and a speaker for Insulet; JR has served on scientific advisory boards and received honoraria or consulting fees from Eli Lilly, Novo Nordisk, Sanofi, Janssen, Boehringer Ingelheim, and Intarcia Therapeutics, and has received grants/research support from Merck, Pfizer, Sanofi, Novo Nordisk, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Boehringer Ingelheim, Intarcia Therapeutics, and Lexicon; MLV was a full-time employee of Bristol-Myers Squibb during the time the study was conducted and completed; EH is an employee of AstraZeneca; HW was a contractor for AstraZeneca during the time the statistical analyses were done; NI is an employee of AstraZeneca.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Patient disposition. ITT, intention to treat; QWS-AI, once-weekly suspension by autoinjector.

Figure 2

Effects of switching from exenatide two times per day to exenatide QWS-AI or continuing exenatide QWS-AI on various measures of efficacy in the modified intention-to-treat population. (A) A1C over time. (B) Proportion of patients achieving A1C goals at weeks 28 and 52. (C) Fasting plasma glucose over time. (D) Body weight over time. A1C, glycated hemoglobin; LS, least squares; QWS-AI, once-weekly suspension by autoinjector.