title: Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial.
abstract: OBJECTIVE
  Patients with type 2 diabetes have an increased risk of bone fractures, the predisposing factors for which are unknown. Treatment with thiazolidinediones (TZDs) further increases the incidence of osteoporotic fractures. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, fractures were considered an adverse event of special interest, and information regarding fractures was collected.
  
  
  METHODS
  We compared the incidence of fractures among the 8,280 patients who were assigned to treatment with saxagliptin with that in the 8,212 patients who were assigned to placebo. We further analyzed the participants' baseline characteristics and fracture risk.
  
  
  RESULTS
  During a median follow-up of 2.1 years, 241 patients (2.9%) in the saxagliptin group and 240 (2.9%) in the placebo group experienced a fracture (hazard ratio [HR] 1.00 [95% CI 0.83-1.19]). Event rates for fractures were the same in both treatment arms: 14.7 per 1,000 patient-years in the entire population and 14.0 in the on-treatment population (first event only). Fracture risk was similar in patients treated with saxagliptin or placebo across different subgroups defined by race, cardiovascular risk, and renal function. A multivariable Cox regression analysis showed that risk of fracture was associated with female sex (P < 0.0001), longer diabetes duration (P < 0.0001), older age (P = 0.002), major hypoglycemic events (P = 0.01), noncompliance with study drug (P = 0.01), and treatment with TZDs (P = 0.03).
  
  
  CONCLUSIONS
  In a large population of older patients with type 2 diabetes, treatment with saxagliptin was not associated with an increased risk of fractures. The association between longer diabetes duration and increased risk of bone fracture is an intriguing finding.
authors.affiliation: Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.affiliation: AstraZeneca, Gaithersburg, MD.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Wei
authors.affiliation: Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Jaime
authors.initials: J
authors.lastname: Davidson
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Yanuv
authors.affiliation: Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Aliza
authors.initials: A
authors.lastname: Rozenberg
authors.affiliation: AstraZeneca Research and Development, Wilmington, DE.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.affiliation: Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Avivit
authors.initials: A
authors.lastname: Cahn
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Stahre
authors.affiliation: Department of Internal Diseases, Diabetology and Cardiometabolic Diseases, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Strojek
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004151:Dipeptides / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications*; D058866:Osteoporotic Fractures / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D004151:Dipeptides; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C502994:saxagliptin; D000218:Adamantane