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

ABSTRACT 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.