Discontinuation of oral semaglutide due to adverse effects: a database study on Japanese individuals with type 2 diabetes

The global prevalence of diabetes continues to rise, necessitating advancements in treatment, such as glucagon-like peptide-1 receptor agonists. While oral semaglutide has demonstrated comparable efficacy to injectable formulations, gastrointestinal symptoms remain a barrier to continued use. This study analyzed factors associated with discontinuation of oral semaglutide due to gastrointestinal symptoms in individuals newly prescribed the drug at Jikei University Hospital between 2022 and 2023. A total of 358 individuals were categorized into discontinuation (n =  65) and continuation (n  = 293) groups based on continuation of treatment for at least 180 days. Logistic regression analyses identified higher HbA1c levels and metformin use as significant predictive factors for discontinuation at 3 mg. Furthermore, individuals taking metformin  ≥  1000 mg/day (high-dose metformin) exhibited a significantly higher risk of discontinuation due to gastrointestinal symptoms. In the supplementary analyses that included individuals who escalated from 3 mg to higher doses, metformin use-regardless of dose-was associated with early gastrointestinal-related discontinuation at 3 mg. No significant predictive factors were identified at 7 mg or 14 mg. These findings suggest that careful consideration should be given when initiating oral semaglutide, particularly in individuals with high HbA1c levels or those receiving metformin therapy.

The online version contains supplementary material available at 10.1007/s13340-025-00868-0.