PMID- 25758769
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 38
IP  - 6
DP  - 2015 Jun
TI  - Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 
      trial.
PG  - 1145-53
LID - 10.2337/dc14-2868 [doi]
AB  - OBJECTIVE: To examine the safety and cardiovascular (CV) effects of saxagliptin 
      in the predefined elderly (>/=65 years) and very elderly (>/=75 years) subpopulations 
      of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with 
      Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. 
      RESEARCH DESIGN AND METHODS: Individuals >/=40 years (n = 16,492; elderly, n = 
      8,561; very elderly, n = 2,330) with HbA1c >/=6.5% (47.5 mmol/mol) and </=12.0% 
      (107.7 mmol/mol) were randomized (1:1) to saxagliptin (5 or 2.5 mg daily) or 
      placebo in a double-blind trial for a median follow-up of 2.1 years. RESULTS: The 
      hazard ratio (HR) for the comparison of saxagliptin versus placebo for the 
      primary end point (composite of CV mortality, myocardial infarction, or ischemic 
      stroke) was 0.92 for elderly patients vs. 1.15 for patients <65 years (P = 0.06) 
      and 0.95 for very elderly patients. The HRs for the secondary composite end 
      points in the entire cohort, elderly cohort, and very elderly cohort were 
      similar. Although saxagliptin increased the risk of hospitalization for heart 
      failure in the overall saxagliptin population, there was no age-based treatment 
      interaction (P = 0.76 for elderly patients vs. those <65 years; P = 0.34 for very 
      elderly patients vs. those <75 years). Among saxagliptin-treated individuals with 
      baseline HbA1c >/=7.6% (59.6 mmol/mol), the mean change from baseline HbA1c at 2 
      years was -0.69%, -0.64%, -0.66%, and -0.66% for those >/=65, <65, >/=75, and <75 
      years old, respectively. The incidence of overall adverse events (AEs) and 
      serious AEs was similar between saxagliptin and placebo in all cohorts; however, 
      hypoglycemic events were higher for saxagliptin versus placebo regardless of age. 
      CONCLUSIONS: The SAVOR-TIMI 53 trial supports the overall CV safety of 
      saxagliptin in a robust number of elderly and very elderly participants, although 
      the risk of heart failure hospitalization was increased irrespective of age 
      category. AEs and serious AEs as well as glycemic efficacy of saxagliptin in 
      elderly patients are similar to those found in younger patients.
CI  - (c) 2015 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Leiter, Lawrence A
AU  - Leiter LA
AD  - Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and 
      Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University 
      of Toronto, Toronto, ON, Canada leiterl@smh.ca.
FAU - Teoh, Hwee
AU  - Teoh H
AD  - Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and 
      Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University 
      of Toronto, Toronto, ON, Canada Division of Cardiac Surgery, Li Ka Shing 
      Knowledge Institute and Keenan Research Centre for Biomedical Science, St. 
      Michael's Hospital, University of Toronto, Toronto, ON, Canada.
FAU - Braunwald, Eugene
AU  - Braunwald E
AD  - TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, MA.
FAU - Mosenzon, Ofri
AU  - Mosenzon O
AD  - Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
FAU - Cahn, Avivit
AU  - Cahn A
AD  - Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
FAU - Kumar, K M Prasanna
AU  - Kumar KM
AD  - Bangalore Diabetes Hospital and Centre for Diabetes and Endocrine Care, Bangalore 
      Diabetes Hospital, Bangalore, India.
FAU - Smahelova, Alena
AU  - Smahelova A
AD  - Department of Internal Gerontometabolic Clinic, Charles University in Prague, 
      Hradec Kralove, Czech Republic.
FAU - Hirshberg, Boaz
AU  - Hirshberg B
AD  - AstraZeneca, Wilmington, DE.
FAU - Stahre, Christina
AU  - Stahre C
AD  - AstraZeneca, Molndal, Sweden.
FAU - Frederich, Robert
AU  - Frederich R
AD  - Bristol-Myers Squibb, Princeton, NJ.
FAU - Bonnici, Francois
AU  - Bonnici F
AD  - UCT Private Academic Hospital, Cape Town, South Africa.
FAU - Scirica, Benjamin M
AU  - Scirica BM
AD  - TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, MA.
FAU - Bhatt, Deepak L
AU  - Bhatt DL
AD  - TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, MA.
FAU - Raz, Itamar
AU  - Raz I
AD  - Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
CN  - SAVOR-TIMI 53 Steering Committee and Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01107886
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150310
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptides)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 9GB927LAJW (saxagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/administration & dosage/adverse effects/*analogs & derivatives
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy/mortality
MH  - Diabetic Angiopathies/mortality
MH  - Dipeptides/*administration & dosage/adverse effects
MH  - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Heart Failure/mortality
MH  - Hospitalization/statistics & numerical data
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/mortality
MH  - Stroke/mortality
MH  - Treatment Outcome
FIR - Braunwald, Eugene
IR  - Braunwald E
FIR - Bhatt, Deepak L
IR  - Bhatt DL
FIR - Raz, Itamar
IR  - Raz I
FIR - Davidson, Jaime A
IR  - Davidson JA
FIR - Frederich, Robert
IR  - Frederich R
FIR - Hirshberg, Boaz
IR  - Hirshberg B
FIR - Steg, Gabriel
IR  - Steg G
EDAT- 2015/03/12 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/03/12 06:00
PHST- 2014/12/02 00:00 [received]
PHST- 2015/02/09 00:00 [accepted]
PHST- 2015/03/12 06:00 [entrez]
PHST- 2015/03/12 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - dc14-2868 [pii]
AID - 10.2337/dc14-2868 [doi]
PST - ppublish
SO  - Diabetes Care. 2015 Jun;38(6):1145-53. doi: 10.2337/dc14-2868. Epub 2015 Mar 10.