Modeling effects of <scp>SGLT</scp>‐2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes

<jats:sec><jats:title>Aims</jats:title><jats:p>Dapagliflozin, a sodium‐glucose cotransporter 2 (<jats:styled-content style="fixed-case">SGLT</jats:styled-content>‐2) inhibitor, has been shown to lower glycated hemoglobin (<jats:styled-content style="fixed-case">HbA1c</jats:styled-content>), weight, blood pressure and serum uric acid in clinical trials. Plasma lipids were also evaluated as exploratory variables. The goal of this study was to estimate the long‐term cardiovascular (<jats:styled-content style="fixed-case">CV</jats:styled-content>) and microvascular outcomes of dapagliflozin added to the standard of care (<jats:styled-content style="fixed-case">SOC</jats:styled-content>) versus <jats:styled-content style="fixed-case">SOC</jats:styled-content> using simulation methodology.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The Archimedes Model, a validated model of human physiology, diseases and healthcare systems, was used to model a type 2 diabetes mellitus (<jats:styled-content style="fixed-case">T2DM</jats:styled-content>) population derived from National Health and Nutrition Examination Survey (<jats:styled-content style="fixed-case">NHANES</jats:styled-content>) with <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> 7–10%, taking a single oral antidiabetic agent [metformin, sulfonylureas <jats:styled-content style="fixed-case">SU</jats:styled-content> or thiazolidinedione (<jats:styled-content style="fixed-case">TZD</jats:styled-content>)] at the beginning of the trial. A 20‐year trial was simulated comparing dapagliflozin 10 mg, given in addition to <jats:styled-content style="fixed-case">SOC</jats:styled-content>, with <jats:styled-content style="fixed-case">SOC</jats:styled-content> alone. <jats:styled-content style="fixed-case">SOC</jats:styled-content> was based on American Diabetes Association (<jats:styled-content style="fixed-case">ADA</jats:styled-content>)/European Association for the Study of Diabetes (<jats:styled-content style="fixed-case">EASD</jats:styled-content>) 2012 guidelines and included diet, metformin, <jats:styled-content style="fixed-case">SU</jats:styled-content>, <jats:styled-content style="fixed-case">TZD</jats:styled-content>, dipeptidyl peptidase‐4 (<jats:styled-content style="fixed-case">DPP</jats:styled-content>‐4), glucagon‐like peptide‐1 (<jats:styled-content style="fixed-case">GLP</jats:styled-content>‐1), and insulin therapies, with usage levels reflective of those in <jats:styled-content style="fixed-case">NHANES</jats:styled-content>. Dapagliflozin effects were derived from phase 3 clinical trial results. End points included <jats:styled-content style="fixed-case">CV</jats:styled-content> and microvascular outcomes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Over a 20‐year period, patients on dapagliflozin were projected to experience relative reductions in the incidence of myocardial infarction (<jats:styled-content style="fixed-case">MI</jats:styled-content>), stroke, <jats:styled-content style="fixed-case">CV</jats:styled-content> death, and all‐cause death of 13.8, 9.1, 9.6 and 5.0%, respectively, and relative reductions in the incidence of end‐stage renal disease (<jats:styled-content style="fixed-case">ESRD</jats:styled-content>), foot amputation, and diabetic retinopathy of 18.7, 13.0 and 9.8%, respectively, when compared with <jats:styled-content style="fixed-case">SOC</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>On the basis of simulation results, adding dapagliflozin to currently available treatment options is projected to further decrease the <jats:styled-content style="fixed-case">CV</jats:styled-content> and microvascular complications associated with <jats:styled-content style="fixed-case">T2DM</jats:styled-content>.</jats:p></jats:sec>