Tirzepatide persistence, adherence, and dose escalation in a real-world setting with high out-of-pocket costs: a Polish cohort study

PURPOSE: Tirzepatide is effective in clinical trials, but its real-world use where obesity pharmacotherapy is self-funded remains poorly characterized. We aimed to characterize tirzepatide persistence, adherence, and dose escalation in a high out-of-pocket-cost setting. PATIENTS AND METHODS: We retrospectively analyzed nationwide electronic health records from a large Polish private healthcare provider. We included 3,030 adults with a first recorded tirzepatide prescription between November 2023 and February 2025. The primary endpoint was time to observed treatment discontinuation. Multivariable Cox regression identified persistence predictors, while adherence was assessed using proportion of days covered (PDC). Successful titration was escalation from 2.5 or 5 mg to ≥10 mg. RESULTS: The cohort included 69.0% women; 83.3% had obesity and 20.0% had type 2 diabetes. Higher first recorded dose was associated with earlier loss of observed treatment. Compared with 2.5 mg initiators, the hazard ratio for discontinuation was 1.44 (95%CI 1.26-1.64, p<0.001) for 15 mg and 1.24 (95%CI 1.12-1.39, p<0.001) for 10 mg doses. Traditional comorbidities did not independently predict persistence (all p>0.10). Among385 patients persistent for ≥180 days, median PDC was 0.86 (IQR 0.73-0.95), with 68% classified as adherent (PDC ≥80%). Of 2,194 eligible low-dose patients, 565 (25.8%) escalated to ≥10 mg, corresponding to 18.6% of the full cohort. CONCLUSIONS: Real-world tirzepatide persistence was suboptimal and associated with recorded starting dose. Traditional clinical comorbidities had limited impact on discontinuation timing. Nonclinical factors, including affordability, tolerability, and patient expectations, may contribute to early loss of observed treatment; although these were not directly measured.