Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study.

Buse JB, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381(9861):117-124.


DURATION (Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention with Exenatide Once-Weekly) is a series of multinational studies comparing once-weekly exenatide with other antihyperglycemic therapies for treatment of type 2 diabetes.

The DURATION-4 study compared once-weekly exenatide with metformin, pioglitazone, and sitagliptin, with results showing once-weekly exenatide to be superior to sitagliptin and noninferior to metformin but not pioglitazone with regard to A1C lowering.1 DURATION-5, which compared once-weekly exenatide to twice-daily exenatide, showed superior A1C lowering with once-weekly exenatide formulation.2 No major hypoglycemia occurred in either study.

DURATION-6 Design  

DURATION-6 is the first head-to-head study comparing two long-acting glucagon-like peptide-1 (GLP-1) receptor agonists—once-weekly exenatide and once-daily liraglutide—for type 2 diabetes treatment.

This open-label, parallel-group study randomized participants to once-daily liraglutide (1.8 mg) or once-weekly exenatide (2 mg) over 26 weeks. The intention-to-treat analysis included 911 subjects, of whom 450 received liraglutide and 461 received exenatide. Subjects had type 2 diabetes suboptimally treated with lifestyle modification and oral antihyperglycemic therapy, A1C 7.1%-11.0%, body mass index ≤45 kg/m2, and stable weight for ≥3 months. A1C change from baseline to Week 26 was the primary endpoint. (Click here for slide.)  


Treatment with both once-weekly exenatide and once-daily liraglutide showed improvements in A1C, with greater mean A1C change seen among liraglutide-treated patients (least-squares mean A1C change: -1.48% [95% confidence interval {CI}, -1.58 to -1.38] vs -1.28% [-1.38 to -1.18]; P=0.02). The treatment difference was 0.21% (95% CI, 0.8-0.33), which did not meet noninferiority criteria set by the study investigators. (Click here for slide.)  

Both liraglutide- and exenatide-treated patients showed decreases in weight* and fasting serum glucose, which were predefined secondary endpoints. Liraglutide-treated patients had greater reductions in both of these parameters. Other secondary endpoints, including blood pressure and cardiovascular biomarkers, showed similar improvements in both groups.* (Click here for slide.)  

Adverse events were primarily gastrointestinal (GI). The most prevalent GI events, nausea, diarrhea, and vomiting, occurred more frequently among liraglutide-treated patients compared with exenatide-treated patients. Incidence of GI events decreased over time in both treatment groups.

A similar number of patients in both treatment groups experienced minor hypoglycemia; no major hypoglycemia occurred. (Click here for slide.)  

*Once-weekly exenatide and liraglutide are not FDA approved for weight loss, or treatment of blood pressure, lipids, C-reactive protein, or brain natriuretic peptide

1. Russell-Jones D, Cuddihy RM, Hanefeld M, et al; for the DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naïve patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012;35(2):252-258.

2. Blevins T, Pullman J, Malloy J, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96(5):1301-1310.

Related content: 

Clinical Insights® in Diabetes :: December 2012  

Overview and slides: DURATION-4  

Expert commentary: Vivian A. Fonseca, MD, explores data from the DURATION-4 study  


December 2012

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Last Modified: 3/23/2015