title: Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION-NEO-2 randomized clinical study.
abstract: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo.
  
  
  
  In this open-label, multicentre study of patients with type 2 diabetes who had suboptimal glycaemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2.0 mg QWS-AI, sitagliptin 100 mg once daily or oral placebo (3:2:1 ratio). The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to 28 weeks.
  
  
  
  At 28 weeks, exenatide QWS-AI significantly reduced HbA1c from baseline compared to sitagliptin (-1.13% vs -0.75% [baseline values, 8.42% and 8.50%, respectively]; P  = .02) and placebo (-0.40% [baseline value, 8.50%]; P = .001). More exenatide QWS-AI-treated patients achieved HbA1c <7.0% than did sitagliptin- or placebo-treated patients (43.1% vs 32.0% and 24.6%; both P  < .05). Exenatide QWS-AI and sitagliptin reduced fasting plasma glucose from baseline to 28 weeks (-21.3 and -11.3 mg/dL) vs placebo (+9.6 mg/dL), with no significant difference between the 2 active treatments. Body weight decreased with both active treatments (-1.12 and -1.19 kg), but not with placebo (+0.15 kg). No improvement in blood pressure was observed in any group. The most common adverse events with exenatide QWS-AI were gastrointestinal events and injection-site reactions.
  
  
  
  This study demonstrated that exenatide QWS-AI reduced HbA1c more than sitagliptin or placebo and was well tolerated.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana.
authors.forename: Kishore M
authors.identifier: 0000-0002-1856-5574
authors.initials: KM
authors.lastname: Gadde
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Marion L
authors.initials: ML
authors.lastname: Vetter
authors.affiliation: AstraZeneca, Gaithersburg, Maryland.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: AstraZeneca, Gaithersburg, Maryland.
authors.forename: Elise
authors.initials: E
authors.lastname: Hardy
authors.affiliation: AstraZeneca, Gaithersburg, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Öhman
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000517:prevention & control; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005079:Excipients / Q000008:administration & dosage / Q000009:adverse effects; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D054795:Incretins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007277:Injections, Jet; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use; D014280:Triglycerides / Q000008:administration & dosage / Q000009:adverse effects; D014481:United States / Q000453:epidemiology; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005079:Excipients; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D008687:Metformin; D010455:Peptides; D000068900:Sitagliptin Phosphate; D014280:Triglycerides; D014688:Venoms; C517652:hemoglobin A1c protein, human; C022834:miglyol 812
keywords: autoinjector; exenatide; once weekly; sitagliptin; suspension; type 2 diabetes