Aim: To compare the risk of cardiovascular risk associated with second-line treatment with dipeptidyl peptidase-4 inhibitors (DPP4i) by analyzing the national health insurance claim database.
Method: The Korean National Health Insurance (NHI) Service is the single payer which covers all Korean citizens and residents. We identified all patients who used sulfonylurea (SU), or DPP4i as a second-line oral anti-diabetic medication added to metformin (MET) therapy between January 2011 and June 2015 in the NHI database. Cox’s proportional hazard models were used to estimate hazard ratios for major CVD event (coronary artery disease, heart failure, stroke, or transient ischemic attack) between users of second-line treatment with different DPP4i (sitagliptin, vildagliptin, saxagliptin, linagliptin, and gemigliptin) compared to people who used SU as a second-line drug. Sex, age, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications, the Charlson’s comorbidity index, and index year were adjusted as potential confounders.
Results: The observed numbers of CVD events (total observed person-time) were 485 (18,778 person-years) for MET+SU, 248 (12,424 person-years) for MET+sitagliptin, 95 (4,989 person-years) for MET+vildagliptin, 60 (3,137 person-years) for MET+saxagliptin, 282 (16,483 person-years) for MET+linagliptin, and 59 (3,342 person-years) for MET+gemigliptin users. Compared to people who used SU as a second-line drug, the fully adjusted hazard ratios for CVD events were 0.89 (95% CI: 0.76–1.04; p = 0.891) for MET+sitagliptin, 0.82 (95% CI: 0.66–1.03; p = 0.086) for MET+vildagliptin, 0.91 (95% CI: 0.70–1.20; p = 0.506) for MET+saxagliptin, 0.72 (95% CI: 0.62–0.83; p< 0.001) for MET+linagliptin and 0.70 (95% CI: 0.53–0.91; p = 0.009) for MET+gemigliptin.
Discussion: In comparison with people who added SU, people who used linagliptin and gemigliptin as a second-line drug were associated with lower risk of cardiovascular disease.

Impact of second-line treatment with dipeptidyl peptidase-4 inhibitors on the risk of cardiovascular disease