Oral Semaglutide in Routine Clinical Practice: 24-Month Real-World Effectiveness, Persistence and Safety in Adults With Type 2 Diabetes.

AIMS: Real-world long-term data on oral semaglutide are limited. We evaluated its 24-month effectiveness, persistence, and safety in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: This retrospective real-world study included 232 adults with T2D initiating oral semaglutide at an Italian diabetes clinic. Changes in HbA1c, body weight, eGFR, urinary albumin-to-creatinine ratio (UACR) and lipid profile were assessed using linear mixed models. The composite endpoint of HbA1c ≤ 7% and ≥ 5% weight loss was assessed over follow-up. Treatment persistence was evaluated by Kaplan-Meier analysis, and predictors of discontinuation by multivariable Cox regression with time-dependent covariates. HbA1c and body weight before and after switching to another GLP1 receptor agonist were also evaluated. RESULTS: Over 24 months, oral semaglutide significantly reduced HbA1c (-0.8%; p < 0.0001) and body weight (-5.7 kg; p < 0.0001). The composite endpoint was progressively achieved by 44.0% of individuals at 24 months. Non-breakfast administration was independently associated with lower HbA1c after adjustment for BMI, age and sex (β = -0.32; p = 0.041). eGFR and UACR remained stable while total and LDL cholesterol decreased significantly (both p < 0.0001). Treatment persistence at 24 months was 68.5% (mean 19.4 months). Among discontinuers, switching to another GLP1 receptor agonist was the most common strategy (36.2%) and resulted in a further HbA1c reduction (Δ = -0.98%; p = 0.005). No safety concerns emerged. CONCLUSIONS: In this real-world cohort, oral semaglutide provided sustained improvements in glycaemic control, body weight, and lipid profile, with preserved renal function and high treatment persistence over 24 months.