Objective: To explore persistence and adherence with once-daily, twice-daily, or once-weekly DPP-4 inhibitors (DPP-4i) in Japanese patients with type 2 diabetes. Methods: This retrospective, longitudinal, observational cohort study used data from the Japanese nationwide hospital-based Medical Data Vision (MDV) administrative claims database. Data were collected for patients given a new DPP-4i prescription between May 2015 and June 2017 with 1-year follow-up until May 2018. Treatment persistence was defined as the total duration of continuous prescription. Adherence to treatment was measured as the proportion of days covered (PDC). Results: A total of 598,419 patients with a prescription for DPP-4i treatment were identified in the MDV database. Of the 39,826 patients who met the inclusion criteria, 82.4% were receiving once-daily DPP-4i, 15.6% twice-daily DPP-4i, and 2.0% once-weekly DPP-4i. Twelve-month persistence rates with once-daily regimens were 66.3% versus 64.7% with twice-daily (p ¼ .1187), and versus 38.8% with once-weekly, regimens (p < .0001) in the overall population (including untreated [UT] and previously treated [PT] patients); 62.8% with once-daily versus 58.3% with twice-daily (p ¼ .0309), and versus 12.3% with once-weekly regimens (p < .0001) in the UT cohort; and 68.6% with once-daily versus 67.9% with twice-daily (p ¼ .5471), and versus 49.1% with once-weekly regimens (p < .0001) in the PT cohort. In the overall population, 97.8% of patients had a mean PDC of 0.97 with once-and twicedaily, and 65.8% of patients had a mean PDC of 0.74 with once-weekly, DPP-4i regimens. Conclusions: Overall, persistence at 12 months was highest in patients receiving once-daily DPP-4i regimens.