title: Frequency of cancer events with saxagliptin in the SAVOR-TIMI 53 trial.
abstract: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial randomized trial of 16,492 patients (placebo, n = 8212; saxagliptin, n = 8280) treated and followed for a median of 2.1 years afforded an opportunity to explore whether there was any association with cancer reported as a serious adverse event. At least one cancer event was reported by 688 patients (4.1%): 362 (4.3%) and 326 (3.8%) in the placebo and saxagliptin arms, respectively (p = 0.13). There were 59 (0.6%) deaths adjudicated as malignancy deaths with placebo and 53 (0.6%) with saxagliptin. Stratification by gender, age, race and ethnicity, diabetes duration, baseline glycated haemoglobin and pharmacotherapy did not show any clinically meaningful differences between the two study arms. The overall number of cancer events and malignancy-associated mortality rates were generally balanced between the placebo and saxagliptin groups, suggesting a null relationship with saxagliptin use over the median follow-up of 2.1 years. Multivariable modelling showed that male gender, dyslipidaemia and current smoking were independent predictors of cancer. These randomized data with adequate numbers of cancer cases are reassuring but limited, by the short follow-up in a trial not designed to test this hypothesis.
authors.affiliation: Division of Endocrinology & Metabolism, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Division of Endocrinology & Metabolism, Li Ka Shing Knowledge Institute, 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, Toronto, ON, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Teoh
authors.affiliation: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Mosenzon
authors.affiliation: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Cahn
authors.affiliation: AstraZeneca, Wilmington, DE, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hirshberg
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: C A M
authors.initials: CA
authors.lastname: Stahre
authors.affiliation: Internal Medicine, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: J B L
authors.initials: JB
authors.lastname: Hoekstra
authors.affiliation: Molecular Medicine and Surgery, Endocrinology, Metabolism and Diabetes, Karolinska Institutet Solna, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Alvarsson
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Im
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University-Medical Center, Jerusalem, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Raz
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000150:complications; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C502994:saxagliptin; D000218:Adamantane
keywords: antihyperglycemic agents; cancer; saxagliptin