Dipeptidyl peptidase-4 inhibitor use is associated with decreased risk of fracture in patients with type 2 diabetes: a population-based cohort study

Abstract

Aims: The aim of this study was to investigate the putative link between dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of fracture in patients with type 2 diabetes.

Methods: This propensity-score-matched population-based cohort study was performed between 2009 and 2013 on patients with type 2 diabetes who were stable metformin users. A total of 3996 patients with type 2 diabetes used DPP-4i as a second-line antidiabetic drug. The same number of matched non-DPP-4i users were followed up until fracture occurrence, health insurance policy termination, or the end of 2013. The incidence rates of overall and cause-specific fractures were estimated based on the Poisson assumption. A multiple Cox proportional hazard model was used to estimate the covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) to determine the association between DPP-4i use and overall and cause-specific fractures stratified by age and sex.

Results: Over a maximum follow-up period of 5 years, 340 DPP-4i users and 419 non-DPP-4i users were newly diagnosed with fractures, yielding incidence rates of 28.03 and 32.04 per 1000 people per year, respectively. The Cox proportional hazard model revealed that DPP-4i use significantly reduced the risk of all-cause fractures and upper extremity fractures, with adjusted HRs of 0.86 (95% CI: 0.74-0.99) and 0.75 (95% CI: 0.59-0.95), respectively. The aforementioned associations of DDP-4i use with fracture were sustained across sex and age stratifications.

Conclusions: The results of this study supported the premise that DPP-4i usage is associated with a reduced risk of all-cause fractures and upper extremity fractures in patients with type 2 diabetes.

Keywords: cohort study; dipeptidyl peptidase-4 inhibitor; fracture; type 2 diabetes.

Figure 1

Flowchart of study cohort enrolment

Figure 2

Comparison of Nelson–Aalen cumulative hazard estimates of the onset of (A) all fractures (ICD‐9‐CM codes 800–820), (B) hip fracture (ICD‐9‐CM codes 820–821), (C) lower extremity fracture (ICD‐9‐CM codes 820–829), and (D) upper extremity fracture (ICD‐9‐CM codes 810–819) between the DPP‐4i and non‐DPP‐4i groups