Exenatide-Dapagliflozin Combination Effective in Type 2 Diabetes

By Reuters Staff

The combination of exenatide once weekly plus dapagliflozin once daily is better than either agent alone for patients with type 2 diabetes inadequately controlled with metformin, according to results from the DURATION-8 trial.

GLP-1 receptor agonists such as exenatide increase insulin secretion, decrease glucagon secretion, slow gastric emptying, and increase satiety, whereas SGLT2 inhibitors such as dapagliflozin increase urinary glucose excretion. Both have been shown to improve glycemic control and contribute to weight loss with low risk of hypoglycemia.

With funding from AstraZeneca, Dr. Juan P. Frias from the National Research Institute in Los Angeles and colleagues tested the combined treatment with exenatide and dapagliflozin versus either agent alone in a 28-week study of 695 patients with type 2 diabetes inadequately controlled with metformin.

The reduction in HbA1c from baseline to week 28, the primary endpoint, was significantly greater in the exenatide-dapagliflozin combination treatment group, compared with exenatide or dapagliflozin alone, the team reports in The Lancet Diabetes & Endocrinology, online September 16.

Patients receiving exenatide plus dapagliflozin were significantly more likely to achieve an HbA1c of less than 7.0% and achieved significantly greater fasting plasma glucose reductions than did patients receiving either drug alone.

They also achieved significantly greater reductions in weight with the combination than with either drug alone, and more patients taking exenatide-dapagliflozin achieved weight losses of 5% or greater.

Combination treatment was associated with a significantly greater reduction in systolic blood pressure than was either drug alone.

These improvements occurred without any episodes of major or minor hypoglycemia and without any unexpected safety findings, the researchers say.

"The present study provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy," they conclude. "Additional data from ongoing studies investigating the sequential addition of an SGLT2 inhibitor to a GLP-1 receptor agonist (e.g., AWARD-10; NCT02597049) will provide further evidence about the use of these classes in combination."

"Cost analyses are needed to establish the cost-effectiveness of this combined treatment approach," the team adds.

An accompanying editorial notes, "Although Frias and colleagues' choice of a population characterized by high baseline HbA1c was probably motivated by an improved chance of identifying substantial absolute reductions in HbA1c, the finding that only 45% of patients in the combination therapy group achieved an HbA1c of less than 7.0% (<53 mmol/mol) after 28 weeks is disappointing."

"Additional analyses assessing target achievement by baseline HbA1c categories would be helpful," Dr. Michael A. Nauck and Dr. Juris J. Meier from St. Josef Hospital, Ruhr-University Bochum, in Bochum, Germany, write.

"GLP-1 receptor agonists, which tended to be coupled with insulin treatment in the past, might want to rethink their partnership status and carefully check the potential for a preferred relationship with SGLT2 inhibitors," the researchers conclude.

AstraZeneca sponsored the trial, employed three of the seven authors, and provided various grants and fees to the other four authors and to both authors of the editorial.

Dr. Frias did not respond to a request for comments.

SOURCE: http://bit.ly/2d7XchF and http://bit.ly/2do5bF6

Lancet Diabetes Endocrinol 2016.

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