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

Diabetes Obes Metab. 2017 Jul;19(7):979-988. doi: 10.1111/dom.12908. Epub 2017 Mar 17.

Abstract

Aims: 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.

Materials and methods: 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.

Results: 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.

Conclusions: This study demonstrated that exenatide QWS-AI reduced HbA1c more than sitagliptin or placebo and was well tolerated.

Trial registration: ClinicalTrials.gov NCT01652729.

Keywords: autoinjector; exenatide; once weekly; sitagliptin; suspension; type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / prevention & control
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Cardiomyopathies / prevention & control
  • Drug Therapy, Combination / adverse effects
  • Excipients / administration & dosage
  • Excipients / adverse effects
  • Exenatide
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Incretins / administration & dosage
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Injections, Jet
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Sitagliptin Phosphate / adverse effects
  • Sitagliptin Phosphate / therapeutic use
  • Triglycerides / administration & dosage
  • Triglycerides / adverse effects
  • United States / epidemiology
  • Venoms / administration & dosage
  • Venoms / adverse effects
  • Venoms / therapeutic use*

Substances

  • Excipients
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Incretins
  • Peptides
  • Triglycerides
  • Venoms
  • hemoglobin A1c protein, human
  • miglyol 812
  • Metformin
  • Exenatide
  • Sitagliptin Phosphate

Associated data

  • ClinicalTrials.gov/NCT01652729