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

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.

• Authors: Carol H Wysham, Julio Rosenstock, Marion L Vetter, Fang Dong, Peter Öhman, Nayyar Iqbal
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 20 Issue 1 Pg. 165-172 (01 2018) ISSN: 1463-1326 [Electronic] England
• PMID: 28685973 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study)
• Copyright: © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• 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

Topics

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