Five-year efficacy and safety data of exenatide once weekly: long-term results from the DURATION-1 randomized clinical trial.

Abstract

OBJECTIVE:

To evaluate the 5-year efficacy and safety of once weekly exenatide.

PATIENTS AND METHODS:

The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) randomized clinical trial consisted of a 30-week controlled phase (2 mg of exenatide once weekly vs 10 μg of exenatide twice daily) with an open-ended uncontrolled extension (once weekly exenatide only) in patients with type 2 diabetes mellitus on background glucose-lowering therapies (April 15, 2006, through February 21, 2012). At week 30, patients initially receiving 10 μg of exenatide twice daily switched to 2 mg of exenatide once weekly. Study end points included changes from baseline in hemoglobin A1c, fasting plasma glucose, weight, lipids, and blood pressure. Long-term safety data included adverse events, liver and renal function, and heart rate.

RESULTS:

Of 258 extension-phase patients, 153 (59.3%) completed 5 years of treatment. Hemoglobin A1c levels were significantly and durably reduced from baseline (least-squares mean, -1.6%; 95% CI, -1.8% to -1.4%; vs -1.9% for exenatide once weekly at week 30), and 65 (43.9%) of 148 patients achieved hemoglobin A1c levels of less than 7.0%. Significant improvements in fasting plasma glucose level (-28.8 mg/dL; 95% CI, -36.2 to -21.5 mg/dL), weight (-3.0 kg; 95% CI, -4.6 to -1.3 kg), lipids, and diastolic blood pressure were observed, with minimal heart rate increase. Frequencies of nausea and injection-site reactions or nodules were decreased vs the initial 30-week controlled phase. Minor hypoglycemia occurred predominantly with sulfonylurea use, and no major hypoglycemia or new safety signals were observed.

CONCLUSION:

Long-term once weekly exenatide treatment was generally well tolerated with sustained glycemic improvement, weight reduction, and improved markers of cardiovascular risk in patients with type 2 diabetes.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00308139.

• Authors: Carol H Wysham, Leigh A MacConell, David G Maggs, Ming Zhou, Peter S Griffin, Michael E Trautmann
• Journal: Mayo Clinic proceedings (Mayo Clin Proc) Vol. 90 Issue 3 Pg. 356-65 (Mar 2015) ISSN: 1942-5546 [Electronic] England
• PMID: 25744115 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Peptides
• Venoms
• Exenatide

Topics

• Blood Glucose (drug effects)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy)
• Exenatide
• Female
• Glycated Hemoglobin (drug effects)
• Humans
• Hypoglycemic Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Peptides (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Venoms (administration & dosage, adverse effects, therapeutic use)