PMID- 24443793
OWN - NLM
STAT- MEDLINE
DCOM- 20150309
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 16
IP  - 7
DP  - 2014 Jul
TI  - Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard 
      diabetes therapy on cardiovascular and microvascular outcomes.
PG  - 628-35
LID - 10.1111/dom.12261 [doi]
AB  - 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.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Dziuba, J
AU  - Dziuba J
AD  - Department of Science, Archimedes, Inc., San Francisco, CA, USA.
FAU - Alperin, P
AU  - Alperin P
FAU - Racketa, J
AU  - Racketa J
FAU - Iloeje, U
AU  - Iloeje U
FAU - Goswami, D
AU  - Goswami D
FAU - Hardy, E
AU  - Hardy E
FAU - Perlstein, I
AU  - Perlstein I
FAU - Grossman, H L
AU  - Grossman HL
FAU - Cohen, M
AU  - Cohen M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20140219
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Sulfonylurea Compounds)
RN  - 0 (Thiazolidinediones)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - 268B43MJ25 (Uric Acid)
RN  - 9100L32L2N (Metformin)
RN  - AA68LXK93C (2,4-thiazolidinedione)
SB  - IM
MH  - Amputation, Surgical
MH  - Benzhydryl Compounds/*therapeutic use
MH  - Blood Glucose/drug effects
MH  - Blood Pressure/drug effects
MH  - Body Weight/drug effects
MH  - Cardiovascular Diseases/etiology/physiopathology/*prevention & control
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy/physiopathology
MH  - Diabetic Angiopathies/etiology/physiopathology/*prevention & control
MH  - Diabetic Retinopathy/prevention & control
MH  - Disease Progression
MH  - Glucosides/*therapeutic use
MH  - Glycated Hemoglobin/drug effects
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Incidence
MH  - Kidney Failure, Chronic/prevention & control
MH  - Metformin/administration & dosage
MH  - Microcirculation/drug effects
MH  - Middle Aged
MH  - Myocardial Infarction/prevention & control
MH  - Nutrition Surveys
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Stroke/prevention & control
MH  - Sulfonylurea Compounds/administration & dosage
MH  - Thiazolidinediones/administration & dosage
MH  - Treatment Outcome
MH  - Uric Acid/metabolism
OTO - NOTNLM
OT  - SGLT2 inhibitor
OT  - antidiabetic drug
OT  - diabetes mellitus
OT  - renal glucose handling
OT  - type 2 diabetes
OT  - weight loss therapy
EDAT- 2014/01/22 06:00
MHDA- 2015/03/10 06:00
CRDT- 2014/01/22 06:00
PHST- 2013/05/23 00:00 [received]
PHST- 2013/07/16 00:00 [revised]
PHST- 2014/01/11 00:00 [accepted]
PHST- 2014/01/22 06:00 [entrez]
PHST- 2014/01/22 06:00 [pubmed]
PHST- 2015/03/10 06:00 [medline]
AID - 10.1111/dom.12261 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2014 Jul;16(7):628-35. doi: 10.1111/dom.12261. Epub 2014 Feb 
      19.