Hemoglobin A1c levels in patients with type 2 diabetes mellitus receiving oral semaglutide with versus without proton pump inhibitors: An exploratory study.

OBJECTIVE: Oral semaglutide contains salcaprozate sodium, which promotes the opening of epithelial tight junctions and increases gastric pH to prevent its degradation; these actions together improve absorption. Proton pump inhibitors (PPIs) increase gastric pH. However, it is unclear whether PPIs affect the absorption of semaglutide and may therefore enhance the blood glucose lowering effect of semaglutide or affect the reduction of hemoglobin A1c (HbA1c). Therefore, this study investigated differences in HbA1c changes and adverse events between those with and without PPI co-administration. MATERIALS AND METHODS: This single-center retrospective study included patients with type 2 diabetes who received oral semaglutide. Patients were categorized into two groups: those on treatment with PPI (w/PPI) and those not on treatment with PPI (without PPI (w/o PPI)). The primary outcome was the change in HbA1c levels at 52 weeks, while the secondary outcomes included changes at 26 weeks and the incidence of adverse events. RESULTS: A total of 66 patients were included. HbA1c reduction at 52 weeks was significantly greater in the w/PPI group (-1.56 ± 0.37%) than in the w/o PPI group (-1.08 ± 0.76%, p = 0.024). The incidences of adverse events were 24.0% and 31.7% in the w/PPI and w/o PPI groups, respectively (p = 0.502). CONCLUSION: HbA1c reduction at 52 weeks was significantly greater in the PPI co-administration group than in the group without PPI. Future research should include larger sample sizes and pharmacokinetic studies to clarify the clinical implications and interactions between oral semaglutide and PPIs.