Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes

Diabetes Obes Metab. 2018 Jan;20(1):165-172. doi: 10.1111/dom.13056. Epub 2017 Aug 22.

Abstract

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 μg) 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/m2 ; 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.

Trial registration: ClinicalTrials.gov NCT01652716.

Keywords: autoinjector; exenatide; glucagon-like peptide-1 receptor agonist; type 2 diabetes.

Publication types

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

MeSH terms

  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cohort Studies
  • Combined Modality Therapy / adverse effects
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / therapeutic use
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / therapy
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / prevention & control
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Cardiomyopathies / prevention & control
  • Drug Administration Schedule
  • Exenatide
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / physiopathology
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use
  • Incretins / administration & dosage*
  • Incretins / adverse effects
  • Incretins / pharmacokinetics
  • Incretins / therapeutic use
  • Injections, Jet
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Patient Dropouts
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Peptides / pharmacokinetics
  • Peptides / therapeutic use
  • Risk Factors
  • Severity of Illness Index
  • Suspensions
  • United States / epidemiology
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Venoms / pharmacokinetics
  • Venoms / therapeutic use

Substances

  • Delayed-Action Preparations
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Incretins
  • Peptides
  • Suspensions
  • Venoms
  • hemoglobin A1c protein, human
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT01652716