BACKGROUND: We describe changes in HbA1c and body-weight and the relationship between drug adherence and clinical response in a large real-world cohort of patients with type 2 diabetes (T2D) treated with subcutaneous semaglutide for up to three years. METHODS: We included adults with T2D registered at Maccabi Healthcare Services, Israel, who initiated subcutaneous semaglutide (August 2019 - June 2022). Adherence, assessed as Proportion of Days Covered (PDC), was based on drug's dispensation. We assessed the absolute change in HbA1c and the relative change in body-weight from baseline. RESULTS: The 23,442 participants (11,513 women) had a mean age of 62.2 years, HbA1c of 7.6 %, and BMI of 33.7 kg/m CONCLUSIONS: Long-term real-world adherence with semaglutide was relatively stable. Semaglutide use was associated with sustained glycemic control and weight reduction in patients with T2D and relatively good baseline glycemic control, especially among those with high adherence, supporting its use for long-term management of T2D.