Combination therapy in patients with type 2 diabetes uncontrolled by metformin

The authors aimed to determine the benefit of treatment with exenatide (Byetta) once weekly and dapagliflozin (Farxiga) once daily compared to exenatide or dapagliflozin alone in type 2 diabetes. 

The authors concluded that the combination treatment improved blood glucose control and reduced weight and blood pressure in type 2 diabetes inadequately controlled by metformin (Glucophage).

Exenatide is a glucagon-like peptide receptor (GLP-1) that increases insulin secretion to result in improved glucose control and reduced body weight. Dapagliflozin is a treatment that decreases the amount of sugar the body absorbs and increases the amount of sugar excreted in the urine. These treatments can be used in type 2 diabetes when other treatments, such as metformin, fail to control the disease. It is not clear whether using these treatments in combination, rather than one at a time, is more effective.

The aim of this study was to determine whether exenatide and dapagliflozin in combination was more effective in treating type 2 diabetes compared to exenatide or dapagliflozin alone.

695 patients were randomly assigned to one of three different groups. 231 patients in group 1 received exenatide plus dapagliflozin. 231 patients in group 2 received exenatide alone. 233 patients in group 3 received dapagliflozin alone. The follow-up time was 28 weeks.

Patients in group 1 experienced significantly reduced HbA1c levels (average blood glucose levels over the past three months) compared to groups 2 and 3. This was noticeable at week 4 of treatment. More patients in group 1 achieved an HbA1c level of less than 7.0% (goal glucose level for type 2 diabetes) compared to either group 2 or 3. Patients in group 1 had significantly greater reductions in fasting blood glucose levels (blood glucose level after a period without food or drink) compared to groups 2 and 3.

Patients in group 1 experienced significantly greater reductions in weight compared to group 2 and 3. A weight loss of more than 5% was experienced more often in patients from group 1 than patients in group 2 or 3. Patients in group 1 also saw a significant reduction in blood pressure compared to groups 2 or 3.

Side effects from treatment were experienced by 57% of group 1, 54% of group 2 and 52% of group 3. The most common side effects were diarrhea, nausea, urinary tract infections and swelling at the site of injection. 

The authors concluded that the combination of exenatide and dapagliflozin improved blood glucose control and reduced weight and blood pressure in type 2 diabetes inadequately controlled by metformin.

This trial was funded by AstraZeneca, the manufacturers of exenatide and dapagliflozin.