PMID- 28685973 OWN - NLM STAT- MEDLINE DCOM- 20180727 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 1 DP - 2018 Jan TI - Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. PG - 165-172 LID - 10.1111/dom.13056 [doi] AB - 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 mug) 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/m(2) ; 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. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wysham, Carol H AU - Wysham CH AUID- ORCID: 0000-0002-3056-0047 AD - Rockwood Clinic, Spokane, Washington. FAU - Rosenstock, Julio AU - Rosenstock J AD - Dallas Diabetes Research Center at Medical City, Dallas, Texas. FAU - Vetter, Marion L AU - Vetter ML AD - Bristol-Myers Squibb, Princeton, New Jersey. FAU - Dong, Fang AU - Dong F AD - AstraZeneca, Gaithersburg, Maryland. FAU - Ohman, Peter AU - Ohman P AD - AstraZeneca, Gaithersburg, Maryland. FAU - Iqbal, Nayyar AU - Iqbal N AD - AstraZeneca, Gaithersburg, Maryland. LA - eng SI - ClinicalTrials.gov/NCT01652716 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20170822 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Delayed-Action Preparations) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Peptides) RN - 0 (Suspensions) RN - 0 (Venoms) RN - 0 (hemoglobin A1c protein, human) RN - 9P1872D4OL (Exenatide) SB - IM MH - Cardiovascular Diseases/complications/epidemiology/prevention & control MH - Cohort Studies MH - Combined Modality Therapy/adverse effects MH - Delayed-Action Preparations/administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism/therapy MH - Diabetic Angiopathies/epidemiology/prevention & control MH - Diabetic Cardiomyopathies/epidemiology/prevention & control MH - Drug Administration Schedule MH - Exenatide MH - Female MH - Glucagon-Like Peptide-1 Receptor/*agonists/metabolism MH - Glycated Hemoglobin/analysis MH - Humans MH - Hyperglycemia/*prevention & control MH - Hypoglycemia/chemically induced/physiopathology/*prevention & control MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - Incretins/*administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - Injections, Jet MH - Intention to Treat Analysis MH - Male MH - Middle Aged MH - Patient Dropouts MH - Peptides/*administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - Risk Factors MH - Severity of Illness Index MH - Suspensions MH - United States/epidemiology MH - Venoms/*administration & dosage/adverse effects/pharmacokinetics/therapeutic use PMC - PMC5724491 OTO - NOTNLM OT - autoinjector OT - exenatide OT - glucagon-like peptide-1 receptor agonist OT - type 2 diabetes COIS- 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. O. are employees of AstraZeneca. F. D. was an employee of AstraZeneca during the development of this manuscript. EDAT- 2017/07/08 06:00 MHDA- 2018/07/28 06:00 PMCR- 2017/12/11 CRDT- 2017/07/08 06:00 PHST- 2017/02/14 00:00 [received] PHST- 2017/06/28 00:00 [revised] PHST- 2017/07/03 00:00 [accepted] PHST- 2017/07/08 06:00 [pubmed] PHST- 2018/07/28 06:00 [medline] PHST- 2017/07/08 06:00 [entrez] PHST- 2017/12/11 00:00 [pmc-release] AID - DOM13056 [pii] AID - 10.1111/dom.13056 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Jan;20(1):165-172. doi: 10.1111/dom.13056. Epub 2017 Aug 22.