A mechanistic modeling platform of SGLT2 inhibition: Implications for type 1 diabetes

Abstract

Abstract Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by abnormally high blood glucose concentrations due to dysfunction of the insulin‐producing beta‐cells in the pancreas. Dapagliflozin, an inhibitor of renal glucose reabsorption, has the potential to improve often suboptimal glycemic control in patients with T1DM through insulin‐independent mechanisms and to partially mitigate the adverse effects associated with long‐term insulin administration. In this work, we have adapted a systems pharmacology model of type 2 diabetes mellitus to describe the T1DM condition and characterize the effect of dapagliflozin on short‐ and long‐term glycemic markers under various treatment scenarios. The developed platform serves as a quantitative tool for the in silico evaluation of the insulin‐glucose‐dapagliflozin crosstalk, optimization of the treatment regimens, and it can be further expanded to include additional therapies or other aspects of the disease.