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.
© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
Publication types
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Clinical Trial, Phase III
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Comparative Study
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Multicenter Study
MeSH terms
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Cardiovascular Diseases / complications
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Cardiovascular Diseases / epidemiology
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Cardiovascular Diseases / prevention & control
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Cohort Studies
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Combined Modality Therapy / adverse effects
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Delayed-Action Preparations / administration & dosage
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Delayed-Action Preparations / adverse effects
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Delayed-Action Preparations / pharmacokinetics
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Delayed-Action Preparations / therapeutic use
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / metabolism
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Diabetes Mellitus, Type 2 / therapy
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Diabetic Angiopathies / epidemiology
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Diabetic Angiopathies / prevention & control
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Diabetic Cardiomyopathies / epidemiology
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Diabetic Cardiomyopathies / prevention & control
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Drug Administration Schedule
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Exenatide
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Female
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Glucagon-Like Peptide-1 Receptor / agonists*
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Glucagon-Like Peptide-1 Receptor / metabolism
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Glycated Hemoglobin / analysis
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Humans
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Hyperglycemia / prevention & control*
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Hypoglycemia / chemically induced
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Hypoglycemia / physiopathology
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Hypoglycemia / prevention & control*
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Hypoglycemic Agents / administration & dosage*
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Hypoglycemic Agents / adverse effects
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / therapeutic use
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Incretins / administration & dosage*
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Incretins / adverse effects
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Incretins / pharmacokinetics
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Incretins / therapeutic use
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Injections, Jet
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Intention to Treat Analysis
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Male
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Middle Aged
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Patient Dropouts
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Peptides / administration & dosage*
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Peptides / adverse effects
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Peptides / pharmacokinetics
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Peptides / therapeutic use
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Risk Factors
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Severity of Illness Index
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Suspensions
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United States / epidemiology
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Venoms / administration & dosage*
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Venoms / adverse effects
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Venoms / pharmacokinetics
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Venoms / therapeutic use
Substances
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Delayed-Action Preparations
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GLP1R protein, human
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Glucagon-Like Peptide-1 Receptor
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Glycated Hemoglobin A
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Hypoglycemic Agents
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Incretins
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Peptides
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Suspensions
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Venoms
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hemoglobin A1c protein, human
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Exenatide
Associated data
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ClinicalTrials.gov/NCT01652716