title: Long-term use of dipeptidyl peptidase-4 inhibitors and risk of fracture: A retrospective population-based cohort study.
abstract: To investigate the association between long-term dipeptidyl peptidase-4 (DPP-4) inhibitor use and risk of fracture among people with type 2 diabetes mellitus (T2DM).
  
  
  
  A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink database (2007-2015), was conducted. All those (N = 328 254) with at least one prescription for a non-insulin antidiabetic drug (NIAD), aged ≥18 years at the time of data collection, were included. Cox proportional hazards models were used to estimate the hazard ratios of any fracture, osteoporotic fracture and hip fracture in DPP-4 inhibitor users compared with those using other NIADs. Analyses were stratified by continuous duration of DPP-4 inhibitor use. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and concomitant drug use.
  
  
  
  Current use of DPP-4 inhibitors was not associated with risk of any fracture (adjusted hazard ratio [HR] 0.99 [95% confidence interval {CI} 0.93-1.06]) as compared with current other NIAD use. Current use of DPP-4 inhibitors was also not associated with risk of osteoporotic or hip fracture. After stratification by continuous duration of DPP-4 inhibitor use the highest category was not associated with any (>4.0-8.5 years of use, adjusted HR 0.99 [95% CI 0.70-1.41]), osteoporotic (>3.0-8.5 years of use, adjusted HR 0.75 [95% CI 0.52-1.09]) or hip (>2.0-8.5 years of use; adjusted HR 1.24 [95% CI 0.85-1.79]) fracture.
  
  
  
  Continuous long-term DPP-4 inhibitor use (defined as >4.0-8.5 years of DPP-4 inhibitor use for any fracture, >3.0-8.5 years for osteoporotic fracture and >2.0-8.5 years for hip fracture was not associated with risk of any, osteoporotic or hip fracture. These findings may be of value for clinical decisions regarding treatment of patients with T2DM, especially those at high risk of fracture.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands.|Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Johanna H M
authors.initials: JH
authors.lastname: Driessen
authors.affiliation: Department of Internal Medicine, Viecuri Medical Centre, Venlo, The Netherlands.|Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.|Biomedical Research Institute, University Hasselt, Hasselt, Belgium.
authors.forename: Joop P W
authors.initials: JP
authors.lastname: van den Bergh
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Hein A W
authors.initials: HA
authors.lastname: van Onzenoort
authors.affiliation: Department of Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.|Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Ronald M A
authors.initials: RM
authors.lastname: Henry
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands.|Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|MRC Epidemiology Lifecourse Unit, Southampton General Hospital, Southampton, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D006620:Hip Fractures / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
keywords: CPRD; DPP-4 inhibitor; cohort-study; fracture; type 2 diabetes mellitus