title: Safety of saxagliptin: rationale for and design of a series of postmarketing observational studies.
abstract: OBJECTIVE
  To describe the design and rationale of a series of postmarketing studies to examine the safety of saxagliptin, an oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus, in real-world settings.
  
  
  METHODS
  We are conducting a series of retrospective cohort studies using two UK (General Practice Research Database, and The Health Improvement Network) and two US (Medicare, HealthCore Integrated Research Database(SM) ) data sources. The primary outcomes of interest will include (i) hospitalization with acute liver failure, (ii) hospitalization for acute kidney injury, (iii) hospitalization for severe hypersensitivity reactions, (iv) hospitalization for severe infections, (v) hospitalization with infections associated with T-lymphocyte dysfunction (i.e., herpes zoster, tuberculosis, or nontuberculous mycobacteria), and (vi) major cardiovascular events. Diagnosis codes for the outcomes of interest will be validated by medical record review within each data source. Projected use and estimated incidence rates of outcomes of interest suggest there will be at least 80% statistical power to detect a minimum hazard ratio of 1.5 for major cardiovascular events, 2.0 for acute kidney injury and severe infections, 2.4 for acute liver failure, and 4.0 for severe hypersensitivity reactions.
  
  
  RESULTS
  Forthcoming.
  
  
  CONCLUSIONS
  This postmarketing safety assessment will provide important information regarding the safety of saxagliptin and could potentially identify important dipeptidyl peptidase-4 inhibitor class effects. The methods described may be useful to others planning similar evaluations.
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6021, USA. vincentl@mail.med.upenn.edu
authors: Vincent
authors: V
authors: Lo Re
authors: Kevin
authors: K
authors: Haynes
authors: Eileen E
authors: EE
authors: Ming
authors: Jennifer
authors: J
authors: Wood Ives
authors: Laura N
authors: LN
authors: Horne
authors: Kimberly
authors: K
authors: Fortier
authors: Dena M
authors: DM
authors: Carbonari
authors: Sean
authors: S
authors: Hennessy
authors: Serena
authors: S
authors: Cardillo
authors: Peter P
authors: PP
authors: Reese
authors: K Rajender
authors: KR
authors: Reddy
authors: David
authors: D
authors: Margolis
authors: Andrea
authors: A
authors: Apter
authors: Stephen E
authors: SE
authors: Kimmel
authors: Jason
authors: J
authors: Roy
authors: Cristin P
authors: CP
authors: Freeman
authors: Hanieh
authors: H
authors: Razzaghi
authors: Crystal N
authors: CN
authors: Holick
authors: Daina B
authors: DB
authors: Esposito
authors: Tjeerd-Pieter
authors: TP
authors: Van Staa
authors: Harshvinder
authors: H
authors: Bhullar
authors: Brian L
authors: BL
authors: Strom
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives*; D016907:Adverse Drug Reaction Reporting Systems / Q000458:organization & administration* / Q000706:statistics & numerical data; D000465:Algorithms; D015331:Cohort Studies; D003257:Consumer Product Safety; D016208:Databases, Factual; D004151:Dipeptides / Q000009:adverse effects*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D023381:Endpoint Determination; D015340:Epidemiologic Research Design; D006801:Humans; D017891:Pharmacoepidemiology / Q000379:methods; D012189:Retrospective Studies; D006113:United Kingdom
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C502994:saxagliptin; D000218:Adamantane