New study suggests triple therapy improves glycemic control.
Researchers are interested in learning about unexplored combination diabetes therapies for the treatment of type 2 diabetes. Specifically, they want to compare the efficacy and safety of treatment with dapagliflozin vs. placebo add-on to saxagliptin plus metformin in patients whose T2DM is inadequately controlled with saxagliptin plus metformin therapy. Therefore, a study was conducted to investigate these factors.
In this study, patients receiving stable metformin (stratum A; screening HbA1c 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a DPP-4 inhibitor (stratum B; screening HbA1c 7.5-10.5% [58-91 mmol/mol]) for 8 weeks or greater received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B, where saxagliptin was replaced any DPP-4 inhibitor).
Patients who had inadequate glycemic control (HbA1c 7.5-10.5 [53-91 mmol/mol]) were randomly allocated to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. Researchers measured outcomes by determining the change in HbA1c from baseline to week 24. In addition, other parameters measured were FPG, 2-hour PPG, body weight, and number of subjects reaching HbA1c less than 7%.
It was found that treatment with dapagliflozin add-on to saxagliptin plus metformin tracked a greater mean HbA1c reduction than placebo (-0.82% vs -0.10%, P < 0.0001). Significantly greater reductions in FPG, 2-hour PPG, and body weight were also observed. Furthermore, greater number of patients achieved an HbA1c less than 7% with treatment with dapagliflozin compared to placebo. Adverse events were comparable across treatment groups, with a minimal general risk of hypoglycemia at roughly one percent. However, it was noted that genital infections resulted in more patients with dapagliflozin treatment (5%) vs. placebo (0.6%).
Authors believe that triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose T2DM was inadequately controlled with saxagliptin plus metformin therapy. Nonetheless, as noted by Diabetes in Control advisory board member Richard K. Bernstein, MD, it is important to understand that these three drugs together decreased HbA1c by only 0.82% or about 33 mg/dL. Therefore, all clinicians should consider identifying appropriate candidates for this therapy, as well as evaluating risk vs. benefit using this combination therapy.
- Triple combination drug therapy with dapagliflozin added to saxagliptin plus metformin seems to improve glycemic control in T2DM.
- Dapagliflozin add-on to saxagliptin plus metformin is well tolerated in patients whose T2DM is inadequately controlled with saxagliptin plus metformin therapy.
- It is important to note that the addition of dapagliflozin to saxagliptin plus metformin decreases HbA1c by only 0.82%; therefore, consideration for appropriate candidates and risk vs. benefit should be evaluated before recommending this triple therapy option to patients.
Mathieu, Chantal, et al. “Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes.” Diabetes Care 38.11 (August 5, 2015): 2009-2017.