A. Increased bioavailability of both drugs when administered together.

B. Less glucose production in the presence of a DPP-4 inhibitor in response to the glucosuria produced by SGLT2 inhibition

C. Increased affinity of the SGLT2 inhibitor to its target  in the renal tubule in the presence of a DPP-4 inhibitor.

Less endogenous glucose production in the presence of a DPP-4 inhibitor in response to the glucosuria produced by SGLT2 inhibition.

The rationale behind combination therapy to treat T2DM is to prevent or attenuate endogenous compensatory mechanisms that maintain homeostasis in response to pharmacologic intervention. For example, SGLT2 inhibition acts on the renal tubule to prevent glucose reabsorption, leading to glucosuria. Glucosuria results in an increase in the rate of endogenous glucose production, which can offset the glucose-lowering affect by ~50%.1

Since one effect of DPP-4 inhibitors is to reduce endogenous glucose production, the complementary actions of the 2 agents taken together may prove to be especially effective in lowering blood glucose.

 Merovci A, Solis-Herrera C, Daniele G, et al. 

Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production

A New Combination Proves Itself in Treatment for Type 2 Diabetes