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Article Abstract
Background: Dipeptidyl peptidase 4 (DPP4) inhibitors, which are widely used antidiabetic medications, may induce the accumulation of bradykinin and substance P, and thus possibly increase the risk for angioedema.
Objective: To assess the risk for angioedema with the use of DPP4 inhibitors compared with other second-line oral antidiabetics (OADs) in patients with type 2 diabetes.
Methods: A cohort study was conducted using a nationwide health care data of South Korea (2010-2022). Patients older than 40 years, with type 2 diabetes, initiating DPP4 inhibitors or other second-line OADs were included. The primary outcome was angioedema, and the secondary outcome was serious angioedema. Hazard ratio and rate difference per 1000 person-years between DPP4 inhibitors and other OADs were estimated within a 1:1 propensity score-matched cohort.
Results: This study included 1,410,173 patients initiating DPP4 inhibitors and 966,137 patients initiating other second-line OADs, 99.1% of whom were not using concomitant angiotensin-converting enzyme inhibitor due to prescription patterns in South Korea. Over a 1.5-year mean follow-up, no difference in the risk for angioedema with the use of DPP4 inhibitors versus OADs was observed (0.47 and 0.48 events per 1000 person-years, respectively), with a hazard ratio of 0.99 (95% CI, 0.89 to 1.12) and a rate difference of -0.01 (95% CI, -0.07 to 0.05) per 1000 person-years, respectively. The risk for serious angioedema did not increase (rate difference, -0.001 [95% CI, -0.006 to 0.004]; hazard ratio, 0.73 [95% CI, 0.15 to 3.65].
Conclusions: In this large cohort study, the use of DPP4 inhibitors, with 99.1% of users not on concomitant angiotensin-converting enzyme inhibitor therapy, was not associated with an increased risk for angioedema compared with other second-line OADs. However, further studies are needed to determine this risk in those on angiotensin-converting enzyme inhibitor treatment.
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| http://dx.doi.org/10.1016/j.jaip.2025.05.060 | DOI Listing |
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