DPP4 Inhibitors Not Linked to Increased Angioedema Risk in Type 2 Diabetes: Study

The retrospective cohort study examined the data of 1,410,173 patients who started DPP4 inhibitor therapy and 966,137 patients who initiated other second-line OADs. The population was selected to prevent confounding from interaction with angiotensin-converting enzyme (ACE) inhibitors, 99.1% of the patients were not on ACE inhibitors at the time of the study. Included patients were more than 40 years of age, had T2D diagnosed, and had initiated either treatment with DPP4 inhibitors or other second-line OADs.

Primary endpoint was any event of angioedema, and secondary endpoint was defined as serious angioedema. A 1:1 propensity score matching strategy was utilized to equilibrate baseline covariates between the two treatment groups. The median follow-up duration was about 1.5 years, in which time hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were determined.

Key Findings

• The research revealed almost equal incidence of angioedema among both groups

• Angioedema occurrences: 0.47 per 1000 person-years in users of DPP4 vs 0.48 per 1000 person-years among other users of OAD

• Hazard Ratio (HR): 0.99 [95% Confidence Interval (CI), 0.89 to 1.12]

• Rate Difference (RD): -0.01 [95% CI, -0.07 to 0.05] per 1000 person-years

For serious angioedema, the analysis also revealed no important difference:

• HR: 0.73 [95% CI, 0.15 to 3.65]

• RD: -0.001 [95% CI, -0.006 to 0.004] per 1000 person-years

These findings indicate that DPP4 inhibitors have no risk for increased either for angioedema or its more dangerous counterparts in real-world diabetic patients not on ACE inhibitors.

In a national study of more than 2 million South Korean patients, DPP4 inhibitors did not pose an increased risk of angioedema or severe angioedema relative to other second-line oral antidiabetic drugs. With 99.1% of the study population without ACE inhibitor use, the findings provide a solid foundation for the ongoing use of DPP4 inhibitors for managing type 2 diabetes. Further studies are needed to investigate these results in populations with co-prescription of ACE inhibitors.

Reference:

Hong, B., Lee, H., Bae, J. H., Cho, Y. M., & Shin, J.-Y. (2025). Risk for angioedema with the use of dipeptidyl peptidase 4 inhibitors: A population-based cohort study. The Journal of Allergy and Clinical Immunology in Practice. https://doi.org/10.1016/j.jaip.2025.05.060