title: Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial.
abstract: 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: 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.
authors.forename: Hwee
authors.initials: H
authors.lastname: Teoh
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.affiliation: Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
authors.forename: Avivit
authors.initials: A
authors.lastname: Cahn
authors.affiliation: Bangalore Diabetes Hospital and Centre for Diabetes and Endocrine Care, Bangalore Diabetes Hospital, Bangalore, India.
authors.forename: K M Prasanna
authors.initials: KM
authors.lastname: Kumar
authors.affiliation: Department of Internal Gerontometabolic Clinic, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Smahelova
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Stahre
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Robert
authors.initials: R
authors.lastname: Frederich
authors.affiliation: UCT Private Academic Hospital, Cape Town, South Africa.
authors.forename: Francois
authors.initials: F
authors.lastname: Bonnici
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000401:mortality; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006333:Heart Failure / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D020521:Stroke / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; C502994:saxagliptin