The risk of fragility fractures in new users of dipeptidyl peptidase-4 inhibitors compared to sulfonylureas and other anti-diabetic drugs: A cohort study

Abstract

Published by Elsevier via http://dx.doi.org/10.1016/j.ces.2017.10.035 © 2017. This final version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Aims Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic “fragility fractures” (upper extremity, hip, spine).Methods The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016. The primary aim was to compare new-users of DPP-4 inhibitors versus new-users of sulfonylureas (SU). The association between DPP-4 inhibitors and incident fractures was estimated using Cox proportional hazards models. Deciles of high-dimensional propensity scores and other anti-diabetic drugs were used as covariates. Results We identified 7993 and 26,636 new-users of DPP-4 inhibitors and SUs, respectively. At cohort entry, the mean age was 58.8, 40% were female, mean diabetes duration was 1.3 years, and 42% had A1c > 9%. Over 9 years (mean follow-up = 1.2 years), the incident rate of fragility fractures was lower among DPP-4 versus SU users (3.0/1000 vs. 5.2/1000 person-years; P-value = 0.007). After adjustment, there was no statistically significant difference in fracture risk (hazard ratio adjusted, aHR = 0.80, 95%CI 0.51–1.24; P-value = 0.3125). In a secondary analysis, DPP-4 inhibitors were not associated with a difference in fracture risk compared to insulin (aHR = 0.91, 95%CI 0.40–2.09); however were associated with a lower fracture risk versus thiazolidinediones (aHR = 0.47, 95%CI 0.26–0.83). Sensitivity analyses supported findings. Conclusions DPP-4 inhibitors are not associated with an increased risk of fragility fractures compared with SUs or insulin; however, are associated with a lower risk versus thiazolidinediones.JMG is supported as a New Investigator Award from the Canadian Institute of Health Research (CIHR) and a Clinician Scientist Award from Diabetes Canada. JRD is supported by a CIHR fellowship in drug safety and effectiveness. SRM holds the Endowed Chair in Patient Health Management supported by the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences at the University of Alberta, Edmonton, Alberta, Canada