Background <p>Semaglutide is an effective antidiabetic agent that is injected weekly to induce weight reduction, and the impact on cardiovascular outcomes is favorable.</p> Objective <p>The aim was to evaluate the persistence of the use of weekly injectable semaglutide in Colombia for 12 months among new users.</p> Methods <p>A retrospective longitudinal follow-up study of a cohort of patients with a new prescription of weekly injectable semaglutide between January and December 2022 and persistence for 365 days was evaluated. Kaplan‒Meier survival analyses were performed to evaluate the survival effect of semaglutide.</p> Results <p>In total, 9356 new users of semaglutide were identified. The average age of the users was 61.6 ± 12.9 years, the main diagnoses were type 2 diabetes mellitus (43.8%) and obesity (41.8%), and 90.8% of them received the 0.25/0.5-mg dose. The mean duration of use was 93.7 ± 76.3 days, but only 13.8% and 0.2% of patients continued the treatment at 6 and 12 months of follow-up, respectively. In total, 35.4% had a prescription for a single month. The other concomitant antidiabetic drugs used were metformin (43.5%), sodium glucose-2 cotransporter inhibitors (38.3%) and insulin (18.2%).</p> Conclusions <p>Most of the patients started semaglutide at the suggested doses to continue with staging; however, the persistence of use was low, which may be related to difficulties in access, education on application methods, drug tolerability, and lack of follow-up by the clinician.</p>