(044) Dipeptidyl Peptidase-4 Inhibitors Use and Risk of Fracture in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Real-World Data

Background: Patients with type 2 diabetes mellitus (T2DM) are more likely to experience fractures due to abnormal bone health. Anti-diabetic drugs have varying effects on bone, and the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on fracture risk is uncertain.

Objectives: To conduct a pairwise meta-analysis (MA) of real-world studies evaluating the effect of DPP-4i on fracture risk in patients with T2DM.

Methods: A systematic search was conducted on PubMed/Medline and Web of Science from inception to December 2023 to identify real-world studies (prospective, retrospective, and case-control) reporting fracture risk and DPP-4i use compared to the control group (non-DPP4i users and other non-insulin anti-diabetics) in T2DM patients. Pairwise MA was carried out using R Software, and a random-effect model was used to calculate the pooled risk ratio (RR) and 95% confidence interval (CI). In addition, a pooled analysis was performed to estimate the incidence rate (per 1000 person-years) of fracture risk among DPP4i-treated T2DM patients. The quality of the included studies was assessed by using the Newcastle Ottawa (NOS) scale.

Results: A total of nine studies, including 3,33,180 T2DM patients were identified. The patients included in the study were aged >50 years, and 44.2% of them were female. Glycosylated hemoglobin level was >6%, and body mass index ranged from 31.5 to 33 kg/m2. The average duration of diabetes was 2.5 years, and the study follow-up was 3.9 years. Osteoporosis was reported in 4.1% of patients as a comorbidity.
From a pooled analysis, the incidence rate of fracture risk among patients using DPP4i was 9.60 (95%CI 1.67-17.54) per 1000 person-years. Overall, DPP4i significantly reduced fracture risk (any) among T2DM patients (RR [95%CI] 0.91 [0.86-0.97, P=0.004] compared to the control group. However, there was no significant association observed with osteoporotic (RR [95%CI] 0.96 [0.86-1.08], P=0.525], hip (RR [95%CI] 0.95 [0.81-1.12], P=0.572], and vertebral (RR [95%CI] 0.94 [0.84-1.05], P=0.273]) fractures. After gender stratification, no significant association with fracture risk was observed in men (RR [95%CI] 0.90 [0.77-1.06], P=0.211]) or women (RR [95%CI] 0.87 [0.71-1.07], P=0.190]). Overall, quality of the included studies was high.

Conclusions: The use of DPP4i was associated with a reduced fracture risk in T2DM patients. However, DPP4i use does not affect site-specific fracture risk. Given the adverse effects of certain anti-diabetic medications on bone health, current findings could be helpful in guiding treatment decisions for patients with T2DM, particularly in high fracture risk population. Further long-term clinical studies are needed to validate current findings.