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. 2023 Mar 13.
doi: 10.1002/psp4.12956. Online ahead of print.

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

Victor Sokolov #  1   2 , Tatiana Yakovleva #  1 , Leonid Stolbov  1 , Robert C Penland  3 , David Boulton  4 , Joanna Parkinson  5 , Weifeng Tang  4
Affiliations

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

Victor Sokolov et al. CPT Pharmacometrics Syst Pharmacol. .

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.

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