AWARD Trial Shows Promise for GLP-1 Agonist

Treatment with the glucagon-like peptide (GLP)-1 receptor agonist dulaglutide resulted in a greater number of patients achieving a target HbA1c level of less than 7% with no weight gain or hypoglycemia compared with patients on four other commonly-used diabetes drugs, according to the results of a study published recently in Diabetes, Obesity and Metabolism.

These results are from a post-hoc analysis of data from the AWARD trials conducted by Kathleen M. Dungan, MD, of The Ohio State University, and colleagues that analyzed a composite endpoint of HbA1c <7.0%, no weight gain, and no hypoglycemia after 26 weeks of treatment. 

The AWARD trials examined the efficacy and safety of dulaglutide as a monotherapy or combination therapy in patients with uncontrolled type 2 diabetes. Results showed that the drug significantly improved patients’ HbA1c  with a low risk for hypoglycemia compared with metformin, sitagliptin, exenatide twice daily, and insulin glargine, and was non-inferior to liraglutide.

The trials included 4,287 patients with type 2 diabetes; 1,424 of these patients were assigned 1.5-mg dulaglutide and 1,124 were assigned 0.75-mg dulaglutide.

At 26 weeks of treatment, between 37% and 58% of patients assigned 1.5-mg dulaglutide and 27% to 49% of patients assigned 0.75-mg dulaglutide achieved the composite endpoint of this analysis compared with 9% to 61% of patients assigned the active comparators.

Specifically, data showed that significantly more patients assigned 1.5-mg dulaglutide were able to achieve the composite endpoint compared with metformin (OR=1.5; 95% CI, 1.0-22; P<0.05), sitagliptin (OR=4.5; 95% CI, 3.0-6.6; P<0.001), exenatide twice daily (OR=2.6; 95% CI, 1.8-3.7; P<0.001), and insulin glargine (OR=7.4; 95% CI, 4.4-12.6; P<0.001).

In addition, a significantly greater proportion of patients were able to achieve the composite endpoint when assigned the 0.75-mg dose of dulaglutide compared with sitagliptin (OR=3.3; 95% CI, 2.2-4.8; P<0.001) and insulin glargine (OR=4.5; 95% CI, 2.7-7.8; P<0.001).

The researchers pointed out that although many patients were able to achieve the individual targets within the composite endpoint, fewer achieved the composite.

“The advantage of using a composite endpoint is that it allows one to more comprehensively define efficacy and safety, particularly when more than one difference in response to therapy is important,” the researchers wrote.

“For comparisons with metformin and exenatide, the composite outcome appears to be driven largely by HbA1c, while in the comparisons with sitagliptin and glargine, it appears to be driven by both HbA1c and weight,” they wrote. “None of the within study comparisons of composite endpoints were significantly influenced by hypoglycaemia in this analysis.”

Dungan and colleagues explained that they did not pool the data from the AWARD trial because background treatments varied across the trials within the AWARD program and could have influenced the results.

Reference: Dungan KM, et al. Achieving the composite endpoint of HbA1c <7.0%, no weight gain, and no hypoglycaemia in the once weekly dulaglutide AWARD program. Diabetes Obes Metab. 12 Sept 2015 [Epub ahead of print].