Article Text
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.
- Glucagon-Like Peptide-1 (GLP-1)
- type 2 diabetes
- glycemic control
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Footnotes
Presented at The 52-week results of this study have not been presented previously.
Contributors CHW, JR, MLV, and NI contributed to the outline of the manuscript and were involved in the writing, discussion, and critical revision of the manuscript, study conduct, and analysis and interpretation of the data. HW contributed to the statistical analysis of the manuscript and the writing, discussion, and critical revision of the manuscript. EH contributed to the outline of the manuscript and was involved in the writing, discussion, and critical revision of the manuscript and the analysis and interpretation of the data.
Funding The DURATION-NEO-1 study was supported by Bristol-Myers Squibb and AstraZeneca. Development of this manuscript was supported by AstraZeneca.
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.
Patient consent for publication Not required.
Ethics approval The study protocol was approved at each study site by the appropriate institutional review board (main study site IRB approval ID MED1-12-198 and MED1-12-389), and the study was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent prior to participation.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data can be made available upon request. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described online (https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure).