Exenatide Once Weekly Versus Liraglutide Once Daily in Patients With Type 2 Diabetes (DURATION-6): A Randomised, Open-Label Study

Study Questions:

What is the comparative efficacy, safety, and tolerability of the glucagon-like peptide-1 (GLP-1) receptor agonists exenatide once weekly and liraglutide once daily in type 2 diabetic patients with inadequate glycemic control despite the prescription of lifestyle modifications and maximum/near maximum doses of oral antihyperglycemic drugs?


This was a 26-week, open-label, randomized, parallel-group, multicenter, international study in which type 2 diabetic patients were randomly assigned to receive injections of once daily liraglutide or once weekly exenatide. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to week 26. Safety endpoints included adverse events.


A total of 911 patients were included in the intention-to-treat analysis (450 liraglutide, 461 exenatide). Both GLP-1 agonists led to improvements in glycemic control; the mean change in HbA1c was greater in patients in the liraglutide group (-1.48%, standard error [SE] 0.05; n = 386) than in those in the exenatide group (n = -1.28%, SE 0.05; n = 390), with the treatment difference (0.21%; 95% confidence interval [CI], 0.08-0.33) not meeting the predefined noninferiority criteria (upper limit of CI <0.25%). The most common adverse events were gastrointestinal, and were twice as common with liraglutide: nausea (93 [21%] in the liraglutide group vs. 43 [9%] in the exenatide group), diarrhea (59 [13%] vs. 28 [6%]), and vomiting (48 [11%] vs. 17 [4%]).


In the first head-to-head comparison of the efficacy, safety, and tolerability of two long-acting GLP-1 receptor agonists for the treatment of type 2 diabetes, both once daily liraglutide and once weekly exenatide led to improvements in glycemic control. Although there was a greater reduction in HbA1c seen with once daily liraglutide when compared with once weekly exenatide, this came at the expense of substantially more gastrointestinal side effects.


The overall difference in HbA1c following treatment with liraglutide and exenatide was small (0.21%; CI, 0.08-0.33), and may not be clinically and practically meaningfully for some providers and patients, especially when placed in the context of substantially more side effects and a medication that requires daily versus weekly administration.

Keywords: Hemoglobin A, Hypoglycemic Agents, Diabetes Mellitus

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