OBJECTIVES: Real world evidence describing persistence and adherence of type 2 diabetes mellitus (T2DM) therapy focusing on combination drugs is limited in Japan. The aim of this study was to compare the treatment persistence and adherence of oral antidiabetic drugs (OADs) between fixed-dose combinations (FDC) and two-pill combination (TPC) therapy in adults with T2DM in Japan. METHODS: Retrospective analyses of adults with T2DM initiating an OAD combination therapy between Jan. 1, 2011 and Dec. 31, 2015 were conducted using the Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases. Patients initiating FDC therapy were matched (1:1) with those initiating TPC therapy (two OADs administered together) by propensity score to account for potential confounding factors. Persistence rates at 12 month were measured using the time from initiation until first discontinuation of the FDC or at least one of the drug class given concomitantly. Adjusted Cox proportional Hazard model (CPHM) was used to compare time to discontinuation between groups. Adherence was measured using the proportions of days covered (PDC) and non-adherence was defined as a PDC≤80%. RESULTS: After matching, 4,502 and 3,022 individuals were selected from JMDC and MDV, respectively (male: 78.0%/63.8%; mean age: 53.4/67.3). The major OAD combinations evaluated was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinedione (TZD) (64.1% [JMDC] and 70.5% [MDV]). Overall, persistent rates were higher in patients receiving FDC compared with TPC therapy (70.4% vs 66.2% [JMDC], 75.6% vs 55.7% [MDV]). In the JMDC population, persistent rates were highest with DPP-4i schedules (67.5–83.5%). Time to discontinuation was significantly longer with biguanide + TZD and DPP-4i + TZD FDC schedules (p<0.05) and adherence rates were ≥80% across all combinations in both databases. CONCLUSIONS: In this study, adults with T2DM treated with combination therapy were more persistent with FDC therapy than with TPC therapy given concomitantly.