Evidence Supports Use of Triple Therapy for Poorly Controlled Type 2 Diabetes

When blood glucose levels prove difficult to control in patients with type 2 diabetes mellitus, it may be time to consider adding a third drug to the treatment regimen.

When blood glucose levels prove difficult to control in patients with type 2 diabetes mellitus, it may be time to consider adding a third drug to the treatment regimen.

Whether it be with one drug or with multiple medications, getting control of patients’ HbA1c levels continues to be a crucial goal in diabetes treatment. Lead author Chantal Mathieu, MD, PhD, and her colleagues presented results from a study that assessed patients with type 2 diabetes who were given saxagliptin and metformin with the add-on dapagliflozin. The findings were revealed at the American Diabetes Association 75th Scientific Sessions in Boston, MA.

“I was actually extremely surprised by what we were able to achieve in 16 weeks with the medication,” Mathieu, of the University Hospital Leuven, told MD Magazine.

In phase 3 of this trial, the team identified efficacy and safety differences in adding DAPA as the third drug or a placebo. Before receiving treatment, the participants were separated into 2 strata based off of their dipeptidyl peptidase-4 (DPP-4) inhibitor use. Stratum A consisted of those with an inadequate glycemic control of 8.0 to 11.5% on metformin for at least 8 weeks at that point, and Stratum B had a range of 7.5 to 10.5% on metformin in addition to a DPP-4 inhibitor for at least 8 weeks.

The study included a lead-in period during which the first group was given saxagliptin 5 mg/d and metformin immediate release for 16 weeks. The second had saxagliptin 5 mg/d and metformin immediate release; however, all DPP-4 inhibitors were swapped for saxagliptin.

“Just by giving patients or switching their DPP-4, there was a decrease by almost 0.5% [in HbA1c],” Mathieu confirmed.

This process was done in order to find uniform patients taking saxagliptin + metformin for the next part of the study.

“Patients in both strata had to have HbA1c 7.0% - 10.5% at week 2 to be eligible for randomization for double-blind treatment,” the authors wrote.

The number of patients dwindled from 483 to 320, mostly due to not meeting the criteria. When it came time for comparison, the dapagliflozin + saxagliptin + metformin group had an HbA1c reduction of 0.82% while the placebo + saxagliptin + metformin only experienced a 0.10% drop.

“Most patients will require additional therapy in an effort to achieve a desired glycemic goal of HbA1c <7%,” the study concluded.

Now that success has been observed in patients on triple therapy, the team is currently working on identifying specific groups that respond more or less to the method. Whether it be patients who are obese, skinny, diagnosed long ago, or just recently, the next phase of the study to gather more specific information is already underway.