Add-On Therapy With DPP-4 Plus SGLT2 Inhibitor Lowered A1c Better Than Either Added Alone


In patients with A1c poorly controlled on metformin, dual add-on therapy with saxagliptin plus dapagliflozin brought more to A1c goals than either drug added alone.

Assigning patients to a triple therapy that combined the DPP-4 inhibitor saxagliptin plus the SGLT2 inhibitor dapagliflozin with background metformin therapy significantly improved glycemic control when compared with the addition of either drug alone, results of a recently published study show.

The study also found that a larger proportion of patients assigned to triple therapy were able to achieve an HbA1c (A1c) goal of less than 7%.

“The new treatment paradigm consisting of triple therapy with dual add-on of saxagliptin and dapagliflozin to metformin appears to be an attractive therapeutic option to safely and effectively bring patients poorly controlled on metformin monotherapy to individualized glycemic goals,” researchers led by Julio Rosenstock, MD, of Dallas Diabetes and Endocrine Center, wrote in Diabetes Care.

Rosenstock and colleagues examined dual add-on therapy in adults with an A1c between 8% and 12% while on metformin 1,500 mg per day or greater. Patients were randomly assigned to saxagliptin plus dapagliflozin (n=179), saxagliptin alone (n=176), or dapagliflozin alone (n=179).

Enrolled patients had a mean baseline A1c of 8.9%. At week 24 of the study, patients assigned to dual add-on therapy had a mean adjusted decrease in A1c of 1.5% compared with a decrease of 0.9% with saxagliptin alone (p<.0001) and a decrease of 1.2% with dapagliflozin alone (P<.02). Almost twice as many patients assigned to the combination add-on therapy were able to achieve an A1c of less than 7% (41%) compared with those assigned saxagliptin alone (18%) or dapagliflozin alone (22%).

Patients in the study had a mean baseline body mass index of 32 kg/m2. Patients assigned to dual add-on therapy had a mean reduction in body weight of 2.1 kg compared with 2.4 kg in the dapagliflozin alone group and no weight change in the saxagliptin alone group.

“In the subgroup of patients with baseline HbA1c of ≥9%, the change in A1c with saxagliptin plus dapagliflozin plus metformin was similar to that seen with dapagliflozin plus metformin, suggesting that the contribution of saxagliptin to the reduction in HbA1c in this subgroup may have been less than was noted for the HbA1c <8% and HbA1c >8% to <9% subgroups,” the researchers wrote. “However, the number of patients was small and the analysis was not powered to make a definitive conclusion about this observation.”

Dapagliflozin is currently approved as an adjunct to diet and exercise in adults with type 2 diabetes and was tested as a monotherapy, as an add-on to metformin, and as an add-on combination with a thiazolidinedione and the DPP4 inhibitor sitagliptin. Saxagliptin is approved as an adjunct to diet and exercise in adults with type 2 diabetes and was tested in combination with metformin and as an add-on combination therapy with a thiazolidinedione and glyburide. 


This study was funded by Bristol-Myers Squibb and AstraZeneca.


Rosenstock J, Hansen L, Zee P, et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: A randomized, double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2014;doi: 10.2337/dc14-1142.


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