Long-term use of dipeptidyl peptidase-4 inhibitors and risk of fracture: A retrospective population-based cohort study

Johanna H. M. Driessen, Joop P. W. van den Bergh, Hein A. W. van Onzenoort, Ronald M. A. Henry, Hubert G. M. Leufkens, Frank de Vries*

*Corresponding author for this work

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Aims: 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).

Methods: 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.

Results: Current use of DPP-4 inhibitors was not associated with risk of any fracture (adjusted hazard ratio [ HR] 0.99 [ 95% confidence interval {Cl} 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% Cl 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% Cl 0.85-1.79]) fracture.

Conclusion: 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.

Original languageEnglish
Pages (from-to)421-428
Number of pages8
JournalDiabetes Obesity & Metabolism
Issue number3
Publication statusPublished - Mar 2017


  • cohort-study
  • CPRD
  • DPP-4 inhibitor
  • fracture
  • type 2 diabetes mellitus

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