Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study.
BACKGROUND
Exenatide is an incretin mimetic that shares glucoregulatory properties with glucagon-like peptide 1 (GLP-1), and improves glycaemic control, with progressive bodyweight reductions, when administered twice a day in patients with type 2 diabetes. We compared the efficacy of a once-weekly formulation of exenatide to that of a twice daily dose.


METHODS
A 30-week, randomised, non-inferiority study compared a long-acting release formulation of exenatide 2 mg administered once weekly to 10 mug exenatide administered twice a day, in 295 patients with type 2 diabetes (haemoglobin A(1c) [HbA(1c)] 8.3% [SD 1.0], mean fasting plasma glucose 9 [SD 2] mmol/L, weight 102 [SD 20] kg, diabetes duration 6.7 [SD 5.0] years). The patients were naive to drug therapy, or on one or more oral antidiabetic agents. The primary endpoint was the change in HbA(1c) at 30 weeks. This study is registered with ClinicalTrials.gov, number NCT00308139.


RESULTS
At 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA(1c) than those given exenatide twice a day (-1.9 [SE 0.1%] vs -1.5 [0.1%], 95% CI -0.54% to -0.12%; p=0.0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA(1c) levels of 7.0% or less (77%vs 61% of evaluable patients, p=0.0039).


CONCLUSIONS
Exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight.
Drucker
Daniel J
DJ
Department of Medicine, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Buse
John B
JB
Taylor
Kristin
K
Kendall
David M
DM
Trautmann
Michael
M
Zhuang
Dongliang
D
Porter
Lisa
L
D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms