Oral versus subcutaneous semaglutide weight loss outcomes after two years among patients with type 2 diabetes in a real-world database

Background: Interest has grown in glucagon-like peptide-1 receptor-agonist (GLP-1 RA) semaglutide long-term outcomes. This retrospective cohort study compared effectiveness of oral and subcutaneous semaglutide for weight loss outcomes in adults with type 2 diabetes (T2D) over a 2-year treatment period. Research design and methods: Weight loss was evaluated through mean percentage change from baseline, proportion achieving at least 5% weight loss and at least 10% weight loss comparing subcutaneous (n = 310) versus oral users (n = 57) and by age group. Results: Subcutaneous users experienced a mean percentage weight loss of 7.5% (16.7 pounds) with 58.7% and 32.9% achieving >= 5% and >= 10% loss, respectively. Oral users lost 4.4% (8.7 pounds) with 50.9% and 17.5% achieving >= 5% and >= 10% loss, respectively. Significant differences existed between formulations in mean percentage weight change (p-value <0.01) and proportion achieving >= 10% loss (p-value = 0.03), but not in proportion achieving >= 5% loss (p-value = 0.34). Outcomes differed by age within oral semaglutide (p-value = 0.02). Regression analyses adjusted for confounders yielded similar findings. Conclusion: Subcutaneous users achieved superior weight loss compared to oral users. Older oral users experienced better weight loss compared to younger users. However, no differences were observed between subcutaneous users.