Aims: The once-weekly administered glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA) semaglutide, has, in clinical trials, demonstrated significant reductions in glycated haemoglobin A_1c (HbA_1c) and body weight in persons with type 2 diabetes. We evaluated the real-world clinical effects of semaglutide once weekly in a hospital-based diabetes out-patient clinic. Methods: This retrospective observational cohort study included persons with type 2 diabetes (n = 119) on a broad range of antidiabetic medicine: GLP-1RA naïve persons (n = 37) and GLP-1RA-experienced persons (n = 82). Person characteristics at inclusion: age [median (quartiles)]: 65 (57, 72) years; body weight 99 (86, 118) kg; body mass index (BMI) 33 (29, 38) kg/m²; HbA_1c 61 (54, 69) mmol/mol/(7.7 (7.1, 8.5) %). Data were collected at baseline and after 3, 6 and 12 months of semaglutide treatment. Data were analysed using a general linear mixed model for repeated measurements. Results: After 12 months, the reductions in HbA_1c were (mean [95% confidence interval]: GLP-1RA naïve: −12.8 [−17.0, −8.5] mmol/mol/ −1.2 [−1.6, −0.8]% (p < 0.01) and GLP-1RA experienced: −6.4 [−9.0, −3.8] mmol/mol/ −0.6 [−0.8, −0.4]% (p < 0.01), respectively. Body weight reductions in GLP-1RA naïve: −5 [−6.9, −3.1] kg (p < 0.01) and GLP-1RA experienced: −3.2 [−4.4, −2.0] kg (p < 0.01), respectively. Seventy-five percent received 1 mg QW semaglutide. Conclusion: We observed effects of semaglutide once weekly on HbA_1c and body weight comparable with the effects observed in clinical studies with fewer persons in our cohort receiving maximum dose of semaglutide.