LAUSR

ABSTRACT Background Dipeptidyl peptidase-4 inhibitors (DPP4is) and metformin are the most frequently prescribed first-line drugs for Japanese patients with type 2 diabetes (T2D). We investigated the risk of cardiovascular events by second-line treatment type in these patients. Research design and methods Patients with T2D, prescribed either metformin or DPP4i as a first-line drug, were identified in claims data from Japanese acute care hospitals. The primary and secondary outcomes were cumulative risks of MI or stroke and of death, respectively, from second-line treatment initiation. Results Patients prescribed first-line metformin or DPP4i was 16,736 and 74,464, respectively. In patients receiving first-line DPP4i, the death incidence was lower in those receiving second-line metformin than in those receiving second-line sulfonylurea (p < 0.001), whereas the primary outcome was not significantly different. No significant differences were observed for either outcome when DPP4is and metformin were used as first- and second-line drugs or vice versa. Conclusions Metformin was suggested to have larger effect to reduce death than sulfonylurea in patients receiving first-line DPP4i. The order of first- and second-line for the DPP4i and metformin combination did not affect the outcomes. Given the nature of the study design, certain limitations, including potential under-adjustment for confounders, should be considered.