Best Evidence Analyses and Commentary

Once Weekly Exenatide Vs Once Daily Liraglutide
Brett Snyderman, PharmD Candidate; Marcus Campbell, BC-ADM

A 26-week, open-label, multi-center, randomized, parallel-group trial sought to compare once weekly exenatide versus once daily liraglutide in patients with type 2 diabetes. The results of the DURATION-6 trial were published in the January 12th issue of The Lancet in the article titled “Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomized, open-label study”. Study authors hypothesized that once weekly exenatide would be at least non-inferior and/or superior to once daily liraglutide in decreasing glycated hemoglobin (HbA1c) from baseline.

 912 patients were randomized 1:1 to receive either once daily liraglutide (1.8mg) or once weekly exenatide (2mg) for 26 weeks. All patients had type 2 diabetes, uncontrolled by lifestyle modification and taking maximum or near maximum doses of oral antihyperglycemic drugs. The primary outcome of the study was change in HbA1c from baseline at 26 weeks. Results showed that once daily liraglutide decreased HbA1c more than once weekly exenatide (-1.48% and -1.28%; p=0.02) and did not demonstrate non-inferiority for once weekly exenatide (95% CI 0.08-0.33). However, both treatment groups did demonstrate a clinically important decrease in HbA1c from baseline. 271 (60%) of subjects receiving liraglutide and 243 (53%) of subjects receiving exenatide achieved HbA1c levels < 7% (p=0.0011). The liraglutide treatment group also demonstrated greater weight loss than the exenatide group (-3.57 and -2.68 kg, p=0.0005) in all patients regardless of body mass index (BMI). Those receiving liraglutide experienced adverse events at a greater frequency than those receiving exenatide; including nausea (21% and 9%), diarrhea (13% and 6%), headache (8% and 6%), and vomiting (11% and 4%).

Clinicians can use the results of this study when evaluating treatment options for uncontrolled type 2 diabetic patients. Although once daily liraglutide demonstrated a greater decrease in HbA1c and BMI than once weekly exenatide, both drugs demonstrated clinically relevant improvements in glycemic control and weight loss. Well-designed randomized controlled trials are needed to further evaluate this comparison.  The pros and cons of each medication should be weighed on an individual basis when choosing the best medication for the patient, including dosing frequency, possible adverse effects, and cost.


  1. Buse JH, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomized, open-label study. The Lancet. Jan 12, 2013. 381:117-124.


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