Once-weekly exenatide vs once- or twice-daily insulin detemir: efficacy and safety in patients with type 2 diabetes

Davies M, Heller S, Sreenan S, et al. Once-weekly exenatide versus once- or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas. Diabetes Care. 2013;36(5):1368-1376.


Type 2 diabetes is often linked to obesity and requires multiple interventions to achieve A1C goals. Thus, treatments that improve glycemia and body weight with low hypoglycemia risk may be more beneficial than treatments that cause weight gain.

The glucagon-like peptide (GLP)-1 receptor agonist, exenatide, has been shown to provide sustained glycemic control without weight gain or hypoglycemia. Exenatide is available in an extended-release formulation that is administered once weekly. Insulin detemir has shown similar or greater improvement in glycemic control, and less weight gain and hypoglycemia compared with other basal insulins.

The current study by Davies and colleagues is the first to compare treatment with once-weekly exenatide and once- or twice-daily insulin detemir in patients with type 2 diabetes inadequately controlled with oral antidiabetes drugs (OADs). (Click here for slide) 


Subjects enrolled in this 26-week, phase 3, randomized, open-label, parallel-arm, active-comparator study were aged ≥18 years and had type 2 diabetes, A1C ≥7.1% to ≤10.0% despite therapy with metformin monotherapy or metformin plus sulfonylurea, stable weight for 3 months, and body mass index 25-45 kg/m2. Randomization was to once-weekly exenatide (2 mg; n=111) or once- or twice-daily insulin detemir (n=105). Any current oral antihyperglycemic therapy was continued. Subjects were stratified by baseline A1C (≥7.0% to <8.5% or ≥8.5% to ≤10.0%). The primary outcome was the proportion of patients with A1C ≤7.0% and ≥1.0 kg weight loss at 26 weeks. Several secondary outcomes, including glycemic control, cardiovascular risk factors, safety, and tolerability, were also assessed. (Click here for slide)  

Results at 26 weeks  

A total of 44.1% of subjects receiving once-weekly exenatide (n=49; 95% CI, 34.7%-53.9%) and 11.4% of those receiving insulin detemir (n=12; 95% CI, 6.0%-19.1%) met the primary endpoint of A1C ≤7.0% and ≥1.0 kg weight loss. Subjects who received once-weekly exenatide were 6.6 times more likely to achieve the primary outcome versus the insulin group (P<0.0001). Higher baseline A1C reduced the chance of achieving the primary endpoint (P<0.05). (Click here for slide)  

The mean change in A1C was -1.3% (95% CI, -1.45% to 1.14%) among participants receiving once-weekly exenatide and -0.88% (95% CI, -1.03% to 0.72%) for the insulin detemir group. The treatment difference between groups was -0.42% (95% CI, -0.63% to -0.21%; P<0.0001). (Click here for slide)  

The proportion of patients who achieved A1C targets were: (Click here for slide)  

  • A1C ≤7.4%: 67% exenatide vs 54% detemir (P=0.0497)
  • A1C ≤7.0%: 51% exenatide vs 34% detemir (P=0.007)
  • A1C ≤6.5%: 28% exenatide vs 8% detemir (P=0.0002)

Mean body weight change was -2.68 kg (-3.4 to -2.0) among patients receiving once-weekly exenatide and +0.8 kg (0.1 to 1.5) for insulin detemir. The treatment difference between groups was -3.5 kg (95% CI, -4.4 to -2.6; P<0.0001). (Click here for slide) 

Note: Study drugs not indicated for weight loss


February 2013

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: 8/5/2014