AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: D Lansing Taylor; Albert Gough; Mark E Schurdak; Lawrence Vernetti; Chakra S Chennubhotla; Daniel Lefever; Fen Pei; James R Faeder; Timothy R Lezon; Andrew M Stern; Ivet Bahar Journal: Handb Exp Pharmacol Date: 2019
Authors: E G Dorsey-Treviño; J G González-González; N Alvarez-Villalobos; V González-Nava; B M Contreras-Garza; A Díaz González-Colmenero; G Rodríguez-Tamez; F J Barrera-Flores; A M Farrell; V M Montori; R Rodriguez-Gutierrez Journal: J Endocrinol Invest Date: 2019-09-05 Impact factor: 4.256
Authors: Tanya Keenan; Wei Zhao; Asif Rasheed; Weang K Ho; Rainer Malik; Janine F Felix; Robin Young; Nabi Shah; Maria Samuel; Nasir Sheikh; Megan L Mucksavage; Omar Shah; Jin Li; Michael Morley; Annika Laser; Nadeem Hayat Mallick; Khan Shah Zaman; Mohammad Ishaq; Syed Zahed Rasheed; Fazal-Ur-Rehman Memon; Faisal Ahmed; Bashir Hanif; Muhammad Shakir Lakhani; Muhammad Fahim; Madiha Ishaq; Naresh Kumar Shardha; Naveeduddin Ahmed; Khalid Mahmood; Waseem Iqbal; Saba Akhtar; Rabia Raheel; Christopher J O'Donnell; Christian Hengstenberg; Winifred März; Sekar Kathiresan; Nilesh Samani; Anuj Goel; Jemma C Hopewell; John Chambers; Yu-Ching Cheng; Pankaj Sharma; Qiong Yang; Jonathan Rosand; Giorgio B Boncoraglio; Shahana Urooj Kazmi; Hakon Hakonarson; Anna Köttgen; Andreas Kalogeropoulos; Philippe Frossard; Ayeesha Kamal; Martin Dichgans; Thomas Cappola; Muredach P Reilly; John Danesh; Daniel J Rader; Benjamin F Voight; Danish Saleheen Journal: J Am Coll Cardiol Date: 2016-02-02 Impact factor: 24.094