(190) Risk of Lung Cancer With Concomitant Use of Angiotensin Converting Enzyme Inhibitors and Dipeptidyl Peptidase 4 Inhibitors: Population Based Cohort Study

Background: Previous studies showed that the use of angiotensin converting enzyme inhibitors (ACEi) was associated with an increased risk of lung cancer, possibly due to their action in increasing the levels of bradykinin and substance P (SP). Dipeptidyl peptidase 4 inhibitors (DPP4i) have also shown to potentiate the levels of bradykinin and SP. However, whether concomitant use of ACEi and DPP4i would further enhance the risk of lung cancer remains uncertain.

Objectives: To evaluate whether the concomitant use of ACEi and DPP4i is associated with an increased risk of lung cancer compared with concomitant use of ACEi and SGLT2i.

Methods: Using the nationwide healthcare data of South Korea between 2010 and 2022, we identified a cohort of adults who firstly received ACEi and then identified a subset of patients firstly prescribed DPP4i or SGLT2 inhibitors (SGLT2i) during the ACEi treatment. The index date was defined as the first date of DPP4i or SGLT2i administration. The primary outcome was incident lung cancer, defined using a previously validated algorithm with an 88.9% positive predictive value and 95.0% sensitivity. Patients were followed from 1 year after the index date until earliest of lung cancer occurrence, death, study end date (31 December 2022), or 1 year after switching between DPP4i and SGLT2i groups. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of lung cancer were estimated after weighting by propensity score fine stratification. Sensitivity analyses following the as treated and intention-to-treat definition, respectively, and introducing 2-year lag time were performed.

Results: Among a total of 42,108 eligible patients initiating ACEi, 35,990 (85.5%) initiated DPP4i and 6,118 (14.5%) initiated SGLT2i. Concomitant use of DPP4i vs. SGLT2i with a ACEi was associated with an elevated risk of lung cancer (2.28 vs. 1.18 events per 1000 person years; HR 1.95, 95% CI 1.09 to 3.49; RD 1.10, 0.50 to 1.70). Results were consistent in multiple sensitivity analyses.

Conclusions: Among adults initiating ACEi, concomitant use of DPP4i was associated with an increased risk of lung cancer compared with SGLT2i. Thus, concomitant use of ACEi and DPP4i poses a significant drug-drug interaction, and this combination of therapy should be used with caution.