Bone Fracture Risk is Not Associated with the Use of Glucagon-Like Peptide-1 Receptor Agonists: A Population-Based Cohort Analysis

J.H.M. Driessen, R.M.A. Henry, H.A.W. van Onzenoort, A. Lalmohamed, A.M. Burden, D. Prieto-Alhambra, C. Neef, H.G.M. Leufkens, F. de Vries

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Abstract

Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk. We conducted a population-based cohort study, with the use of data from the Clinical Practice Research Datalink (CPRD) database (2007-2012). The study population (N = 216,816) consisted of all individuals with type 2 diabetes patients with at least one prescription for a non-insulin anti-diabetic drug and were over 18 years of age. Cox proportional hazards models were used to estimate the hazard ratio of fracture in GLP1-ra users versus never-GLP1-ra users. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and the use of other drugs. There was no decreased risk of fracture with current use of GLP1-ra compared to never-GLP1-ra use (adjusted HR 0.99, 95 % CI 0.82-1.19). Osteoporotic fracture risk was also not decreased by current GLP1-ra use (adjusted HR 0.97; 95 % CI 0.72-1.32). In addition, stratification according to cumulative dose did not show a decreased bone fracture risk with increasing cumulative GLP1-ra dose. We showed in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs. Future research is needed to elucidate the potential working mechanisms of GLP1-ra on bone.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalCalcified Tissue International
Volume97
Issue number2
DOIs
Publication statusPublished - Aug 2015

Keywords

  • GLP1-ra
  • Fracture
  • Diabetes mellitus type 2
  • Cohort study
  • CPRD
  • DIPEPTIDYL PEPTIDASE-4 INHIBITORS
  • RANDOMIZED CLINICAL-TRIALS
  • MINERAL DENSITY
  • EUROPEAN COUNTRIES
  • DIABETES-MELLITUS
  • HIP-FRACTURES
  • CELL-LINE
  • METAANALYSIS
  • WOMEN
  • VALIDATION

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