Inverse association between DPP-4 inhibitor use and fracture in older adults: A disproportionality analysis of the FAERS and JADER.

Objective: Fractures are significantly associated with increased morbidity and mortality in older individuals; additionally, patients with diabetes mellitus are highly prone to fractures. The aim of the present study was to examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and the risk of fracture in older patients by analyzing data obtained from spontaneous adverse event reporting databases from the United States and Japan.

Materials and methods: Data on older patients registered in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the end of 2019 and data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to December 2019 were used. Reporting odds ratio (ROR) and information component (IC) values were used for disproportionality analysis.

Results: Significant inverse associations between DPP-4 inhibitor use and fracture were found for DPP-4 inhibitors as a whole (ROR = 0.80; 95% CI = 0.73 - 0.88; IC = -0.31, 95% CI = -0.46 to -0.17); linagliptin (ROR = 0.74; 95% CI = 0.59 - 0.94; IC = -0.42, 95% CI = -0.75 to -0.08); and sitagliptin (ROR = 0.77; 95% CI = 0.68 - 0.88; IC = -0.36, 95% CI = -0.55 to -0.17) in the analyses of FAERS data. Similarly, significant inverse associations were also found for DPP-4 inhibitors as whole (ROR = 0.71; 95% CI = 0.59 to 0.86; IC = -0.46, 95% CI = -0.74 to -0.18); sitagliptin (ROR = 0.70; 95% CI = 0.52 - 0.95; IC = -0.49, 95% CI = -0.93 to -0.05); and vildagliptin (ROR = 0.54; 95% CI = 0.35 - 0.83; IC = -0.85, 95% CI = -1.49 to -0.22) in the analyses of JADER data.

Conclusion: Our analysis of adverse event databases using different algorithms revealed that DPP-4 inhibitor use was inversely associated with fracture in older patients.