title: Predisposing Factors for Any and Major Hypoglycemia With Saxagliptin Versus Placebo and Overall: Analysis From the SAVOR-TIMI 53 Trial.
abstract: To analyze the impact of adding saxagliptin versus placebo on the risk for hypoglycemia and to identify predictors of any and major hypoglycemia in patients with type 2 diabetes included in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study.
  
  
  
  Patients with type 2 diabetes (n = 16,492) were randomized to saxagliptin or placebo and followed for a median of 2.1 years. Associations between any hypoglycemia (symptomatic or glucose measurement <54 mg/dL) or major hypoglycemia (requiring extended assistance) and patient characteristics overall and by treatment allocation were studied.
  
  
  
  At least one hypoglycemic event was reported in 16.6% of patients, and 1.9% reported at least one major event. Patients allocated to saxagliptin versus placebo experienced higher rates of any (hazard ratio [HR] 1.16 [95% CI 1.08, 1.25]; P < 0.001) or major (HR 1.26 [1.01, 1.58]; P = 0.038) hypoglycemia. Hypoglycemia rates (any or major) were increased with saxagliptin in patients taking sulfonylureas (SURs) but not in those taking insulin. Rates were increased with saxagliptin in those with baseline HbA1c ≤7.0% and not in those with baseline HbA1c >7.0%. Multivariate analysis of the overall population revealed that independent predictors of any hypoglycemia were as follows: allocation to saxagliptin, long duration of diabetes, increased updated HbA1c, macroalbuminuria, moderate renal failure, SUR use, and insulin use. Predictors of major hypoglycemia were allocation to saxagliptin, advanced age, black race, reduced BMI, long duration of diabetes, declining renal function, microalbuminuria, and use of short-acting insulin. Among SURs, glibenclamide was associated with increased risk of major but not any hypoglycemia.
  
  
  
  The identification of patients at risk for hypoglycemia can guide physicians to better tailor antidiabetic therapy.
authors.affiliation: Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel Endocrinology and Metabolism Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Avivit
authors.initials: A
authors.lastname: Cahn
authors.affiliation: Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel ntv502@netvision.net.il.
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.affiliation: Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.affiliation: Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel Endocrinology and Metabolism Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Leibowitz
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, Gaithersburg, MD.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: MedImmune, Gaithersburg, MD.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Sjostrand
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Stahre
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: KyungAh
authors.initials: K
authors.lastname: Im
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Estella
authors.initials: E
authors.lastname: Kanevsky
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: 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: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects; D061266:Insulin, Short-Acting / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000139:chemically induced / Q000517:prevention & control; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000218:Adamantane; D004151:Dipeptides; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061266:Insulin, Short-Acting; D013453:Sulfonylurea Compounds; C502994:saxagliptin