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Diabetes Obes Metab. 2014 Jul;16(7):628-35. doi: 10.1111/dom.12261. Epub 2014 Feb 19.

Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes.

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Department of Science, Archimedes, Inc., San Francisco, CA, USA.



Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, has been shown to lower glycated hemoglobin (HbA1c), 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 (CV) and microvascular outcomes of dapagliflozin added to the standard of care (SOC) versus SOC using simulation methodology.


The Archimedes Model, a validated model of human physiology, diseases and healthcare systems, was used to model a type 2 diabetes mellitus (T2DM) population derived from National Health and Nutrition Examination Survey (NHANES) with HbA1c 7-10%, taking a single oral antidiabetic agent [metformin, sulfonylureas SU or thiazolidinedione (TZD)] at the beginning of the trial. A 20-year trial was simulated comparing dapagliflozin 10 mg, given in addition to SOC, with SOC alone. SOC was based on American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) 2012 guidelines and included diet, metformin, SU, TZD, dipeptidyl peptidase-4 (DPP-4), glucagon-like peptide-1 (GLP-1), and insulin therapies, with usage levels reflective of those in NHANES. Dapagliflozin effects were derived from phase 3 clinical trial results. End points included CV and microvascular outcomes.


Over a 20-year period, patients on dapagliflozin were projected to experience relative reductions in the incidence of myocardial infarction (MI), stroke, CV 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 (ESRD), foot amputation, and diabetic retinopathy of 18.7, 13.0 and 9.8%, respectively, when compared with SOC.


On the basis of simulation results, adding dapagliflozin to currently available treatment options is projected to further decrease the CV and microvascular complications associated with T2DM.


SGLT2 inhibitor; antidiabetic drug; diabetes mellitus; renal glucose handling; type 2 diabetes; weight loss therapy

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