AbstractBackgroundWe evaluated the effect of a dipeptidyl peptidase‐4 inhibitor (DPP‐4i) on the progression of obstructive coronary artery disease (OCAD) in patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy.MethodsUsing a multicenter clinical data warehouse, we analyzed the patients receiving insulin therapy for T2DM who underwent coronary computed tomography angiography (CCTA) for ≥2 times. The patients were divided into two groups according to the presence of DPP‐4i prescription between the two CCTA examinations. The prevalence of OCAD (>50% stenosis on CCTA), new revascularization rates, and changes in the coronary calcium score (CCS) were analyzed.ResultsA total of 623 patients were included, and a DPP‐4i was prescribed to 380 (60.9%) patients. The median time difference between the two CCTAs was 39.0 (17.0–61.4) months. Newly developed OCAD at the follow‐up CCTA was detected in 62 (16.3%) patients in the DPP‐4i group and 76 (31.3%) patients in the no DPP‐4i group (p < 0.001). The risk of new OCAD or new revascularization was lower in the DPP‐4i group (19.7% vs. 38.7%; p < 0.001). After propensity score matching, the prevalence of new OCAD (15.9% vs. 29.5%; p = 0.001) and the composite rate of new OCAD or new revascularization (18.7% vs. 37.3%; p < 0.001) were lower in the DPP‐4i group. The change in CCS per year did not differ significantly between the two groups (9.1 [0.1–56.8] vs. 13.5 [0.0–78.6]; p = 0.715).ConclusionsAdd‐on DPP‐4i therapy would be beneficial in preventing coronary artery disease progression in patients with T2DM receiving insulin therapy.