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

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.

Automated summary

Type 1 diabetes mellitus (T1DM) is characterized by high blood glucose concentrations due to dysfunction of insulin-producing beta-cells. Dapagliflozin, a glucose reabsorption inhibitor, has shown potential in improving glycemic control and mitigating adverse effects in T1DM. A systems pharmacology model was adapted to describe T1DM and evaluate the effects of dapagliflozin under different treatment scenarios. This model serves as a useful tool for studying the insulin-glucose-dapagliflozin crosstalk and optimizing treatment regimens.