Impact of co-administration of proton pump inhibitors on efficacy and safety of oral semaglutide in patients with type 2 diabetes: a single-center retrospective study
4 affiliations
- 1Laboratory of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526 Japan
- 2Laboratory of Clinical Pharmacokinetics, Research Support Center, Shizuoka General Hospital, 4-27-1 Kita-ando, Aoi-ku, Shizuoka City, Shizuoka 420-8527 Japan
- 3Laboratory of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuokaï, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526 Japan
- 4Laboratory of Clinical Pharmacogenomics, Research Support Center, Shizuoka General Hospital, 4-27-1 Kita-ando, Aoi-ku, Shizuoka City, Shizuoka 420-8527 Japan
Abstract
Background: Oral semaglutide, a glucagon-like peptide-1 receptor agonist, improves glycemic control and reduces body weight in patients with type 2 diabetes. Although proton pump inhibitors (PPIs) have been reported to slightly increase the absorption of oral semaglutide, the impact of 24-week co-administration of PPIs on clinical efficacy and safety remains unclear.
Methods: This retrospective study included patients with type 2 diabetes who initiated treatment with oral semaglutide between March 2021 and August 2024. The primary outcome was the change in the HbA1c at week 24. The secondary outcomes included the change in body weight and discontinuation of oral semaglutide due to gastrointestinal adverse events at week 24. Patients were divided into two groups according to PPI co-administration. Propensity score matching was performed to balance the baseline characteristics between the groups. Changes in HbA1c and body weight were analyzed using a linear mixed-effects model, and discontinuation rates were compared using Fisher’s exact test.
Results: Among the 114 eligible patients, 30 received concomitant PPIs. After propensity score matching, 27 patients were included in each group. At week 24, the estimated mean change in HbA1c and body weight (95% confidence interval) was − 1.0% (-1.3 to -0.6) and − 1.4 kg (-2.6 to -0.3) in the PPI group and − 0.6% (-0.8 to -0.3) and − 1.8 kg (-2.5 to -1.0) in the non-PPI group. There were no statistically significant group-by-time interactions for HbA1c and body weight (P for interaction = 0.097 and 0.431, respectively). Discontinuation due to gastrointestinal adverse events did not differ significantly between the groups (25.9% vs. 18.5%).
Conclusions: 24-week co-administration of PPIs may not significantly affect the glycemic efficacy, weight reduction, or gastrointestinal tolerability of oral semaglutide. These findings suggest that the co-administration of PPIs is unlikely to meaningfully impact the clinical efficacy or tolerability of oral semaglutide in routine practice.
Related
- Efficacy of adjunctive oral Janus kinase inhibitors in hospitalized patients with extensive or difficult-to-control drug eruptions: a retrospective observational case series
- Clinical Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors After Transcatheter Aortic Valve Replacement in Patients With Diabetes: A Global Retrospective Study
- Short-term clinical efficacy and recorded adverse events of semaglutide combined with dapagliflozin in patients with type 2 diabetes mellitus and chronic kidney disease
- A retrospective real-world study on semaglutide effectiveness in patients with obesity: differences between patients with and without food craving
- Efficacy of phosphodiesterase-3 (PDE-3) inhibitors for the treatment of cerebral vasospasm in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to the intensive care unit (ICU): a systematic review and meta-analysis protocol
BibTeX
@article{yokoyama2026impact,
title = {{Impact of co-administration of proton pump inhibitors on efficacy and safety of oral semaglutide in patients with type 2 diabetes: a single-center retrospective study}},
author = {Tasuku Yokoyama and Tomonobu Uchino and Yasuharu Yazawa and Shohei Ueno and Daiki Tsuji},
journal = {Journal of Pharmaceutical Health Care and Sciences},
year = {2026},
month = aug,
doi = {10.1186/s40780-026-00617-8},
url = {https://doi.org/10.1186/s40780-026-00617-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of co-administration of proton pump inhibitors on efficacy and safety of oral semaglutide in patients with type 2 diabetes: a single-center retrospective study
AU - Tasuku Yokoyama
AU - Tomonobu Uchino
AU - Yasuharu Yazawa
AU - Shohei Ueno
AU - Daiki Tsuji
PY - 2026
DA - 2026/08/05
JO - Journal of Pharmaceutical Health Care and Sciences
DO - 10.1186/s40780-026-00617-8
UR - https://doi.org/10.1186/s40780-026-00617-8
AB - Background: Oral semaglutide, a glucagon-like peptide-1 receptor agonist, improves glycemic control and reduces body weight in patients with type 2 diabetes. Although proton pump inhibitors (PPIs) have been reported to slightly increase the absorption of oral semaglutide, the impact of 24-week co-administration of PPIs on clinical efficacy and safety remains unclear. Methods: This retrospective study included patients with type 2 diabetes who initiated treatment with oral semaglutide between March 2021 and August 2024. The primary outcome was the change in the HbA1c at week 24. The secondary outcomes included the change in body weight and discontinuation of oral semaglutide due to gastrointestinal adverse events at week 24. Patients were divided into two groups according to PPI co-administration. Propensity score matching was performed to balance the baseline characteristics between the groups. Changes in HbA1c and body weight were analyzed using a linear mixed-effects model, and discontinuation rates were compared using Fisher’s exact test. Results: Among the 114 eligible patients, 30 received concomitant PPIs. After propensity score matching, 27 patients were included in each group. At week 24, the estimated mean change in HbA1c and body weight (95% confidence interval) was − 1.0% (-1.3 to -0.6) and − 1.4 kg (-2.6 to -0.3) in the PPI group and − 0.6% (-0.8 to -0.3) and − 1.8 kg (-2.5 to -1.0) in the non-PPI group. There were no statistically significant group-by-time interactions for HbA1c and body weight (P for interaction = 0.097 and 0.431, respectively). Discontinuation due to gastrointestinal adverse events did not differ significantly between the groups (25.9% vs. 18.5%). Conclusions: 24-week co-administration of PPIs may not significantly affect the glycemic efficacy, weight reduction, or gastrointestinal tolerability of oral semaglutide. These findings suggest that the co-administration of PPIs is unlikely to meaningfully impact the clinical efficacy or tolerability of oral semaglutide in routine practice.
SN - 2055-0294
ER -