Comparing medication persistence with oral and subcutaneous semaglutide in a real-world setting

Aims: To compare medication persistence and efficacy of oral and subcutaneous semaglutide, in a real-world setting. Materials and methods: This is a single-center, retrospective observational cohort study. Patients with type 2 diabetes mellitus (T2DM) starting treatment with either formulation of semaglutide between January 1 2019 and July 31 2023 and with at least one follow-up visit were included. The primary endpoint was the difference in the proportion of patients that continued treatment after 6, 12 and 18 months. Main secondary endpoints were change in HbA1c and body weight. Results: We included 242 patients on oral (n = 121) and subcutaneous (n = 121) semaglutide. At baseline, patients in the oral semaglutide group were significantly older (mean age: 67 ± 11 vs. 63 ± 11 years, p = 0.002) and had a lower body mass index (BMI: 30.5 ± 5.6 vs. 33.9 ± 7.1 kg/m2, p < 0.001). The proportion of patients persistent to treatment was significantly lower in the oral group at 6 (85.3% vs. 94.8%; p < 0.001), 12 (72.3% vs. 92.4%, p < 0.001) and 18 (46.0% vs. 83.8%; p < 0.001) months. Most common reasons for discontinuation were gastro-intestinal side effects. When adjusted for age and BMI, body weight and HbA1c reduction were not significantly different between the two formulations, as the proportion of patients achieving the composite outcome of weight loss ≥ 5% and HbA1c < 7.0%. Conclusions: The present real-world study suggests that persistence is significantly lower when semaglutide is administered as a once-daily tablet compared with a weekly injection, while there are no differences in efficacy between the two formulations.