Parasympathetic dysfunction assessed by deep-breathing CVR-R is associated with early discontinuation of oral semaglutide in type 2 diabetes: A multicenter retrospective study.
- 1Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
- 2Department of Diabetes and Endocrine Medicine, Kagoshima Takaoka Hospital, Kagoshima, Japan.
- 3Department of Diabetes and Endocrine Medicine, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.
Abstract
Aims/introduction
Although glucagon-like peptide-1 receptor agonists are widely used for type 2 diabetes, gastrointestinal intolerance frequently leads to early discontinuation. Predictors of oral semaglutide discontinuation remain poorly defined, and its formulation-specific dependence on gastric conditions may influence tolerability. We examined whether the coefficient of variation of R-R intervals (CVR-R) was associated with discontinuation within 6 months.Materials and methods
In this multicenter retrospective study, 203 consecutive patients initiating oral semaglutide between February 2021 and December 2024 were screened, and 61 were analyzed after exclusions. The Discontinuation Group (n = 21) discontinued because of nausea and/or vomiting within 6 months, whereas the Maintenance Group (n = 40) continued for ≥ 6 months. CVR-R was assessed at rest (CVR-R_rest) and during deep breathing (CVR-R_DB). Associations with discontinuation were evaluated using multivariable logistic regression; exploratory machine learning and time-to-event analyses were performed.Results
CVR-R_DB was lower in the Discontinuation Group than in the Maintenance Group (median 1.93% vs 3.26%, P < 0.001). CVR-R_DB remained independently associated with discontinuation after adjustment for age and sex (adjusted OR 0.191; 95% CI 0.071-0.512; P = 0.001; AUC 0.832) and further adjustment for neuropathy stage. The AUC was numerically higher for the age- and sex-adjusted model containing CVR-R_DB than for that containing CVR-R_rest (0.832 vs 0.699; DeLong P = 0.085). An internally derived CVR-R_DB cutoff of 2.55% stratified 6-month persistence (43.3% vs 87.1%; log-rank P < 0.001), and machine learning analyses prioritized CVR-R_DB.Conclusions
Lower CVR-R during deep breathing was associated with early oral semaglutide discontinuation due to nausea and/or vomiting. CVR-R_DB may support risk stratification at initiation.
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BibTeX
@article{ogiso2026parasympathetic,
title = {{Parasympathetic dysfunction assessed by deep-breathing CVR-R is associated with early discontinuation of oral semaglutide in type 2 diabetes: A multicenter retrospective study.}},
author = {Kazuma Ogiso and Takahisa Deguchi and Shigeru Kawade and Aiko Arimura and Yoshihiko Nishio and Katsutaro Morino},
journal = {Journal of diabetes investigation},
year = {2026},
month = oct,
doi = {10.1111/jdi.70477},
url = {https://europepmc.org/article/MED/42921716},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Parasympathetic dysfunction assessed by deep-breathing CVR-R is associated with early discontinuation of oral semaglutide in type 2 diabetes: A multicenter retrospective study.
AU - Kazuma Ogiso
AU - Takahisa Deguchi
AU - Shigeru Kawade
AU - Aiko Arimura
AU - Yoshihiko Nishio
AU - Katsutaro Morino
PY - 2026
DA - 2026/10/24
JO - Journal of diabetes investigation
DO - 10.1111/jdi.70477
UR - https://europepmc.org/article/MED/42921716
AB - Aims/introduction Although glucagon-like peptide-1 receptor agonists are widely used for type 2 diabetes, gastrointestinal intolerance frequently leads to early discontinuation. Predictors of oral semaglutide discontinuation remain poorly defined, and its formulation-specific dependence on gastric conditions may influence tolerability. We examined whether the coefficient of variation of R-R intervals (CVR-R) was associated with discontinuation within 6 months.Materials and methods In this multicenter retrospective study, 203 consecutive patients initiating oral semaglutide between February 2021 and December 2024 were screened, and 61 were analyzed after exclusions. The Discontinuation Group (n = 21) discontinued because of nausea and/or vomiting within 6 months, whereas the Maintenance Group (n = 40) continued for ≥ 6 months. CVR-R was assessed at rest (CVR-R_rest) and during deep breathing (CVR-R_DB). Associations with discontinuation were evaluated using multivariable logistic regression; exploratory machine learning and time-to-event analyses were performed.Results CVR-R_DB was lower in the Discontinuation Group than in the Maintenance Group (median 1.93% vs 3.26%, P < 0.001). CVR-R_DB remained independently associated with discontinuation after adjustment for age and sex (adjusted OR 0.191; 95% CI 0.071-0.512; P = 0.001; AUC 0.832) and further adjustment for neuropathy stage. The AUC was numerically higher for the age- and sex-adjusted model containing CVR-R_DB than for that containing CVR-R_rest (0.832 vs 0.699; DeLong P = 0.085). An internally derived CVR-R_DB cutoff of 2.55% stratified 6-month persistence (43.3% vs 87.1%; log-rank P < 0.001), and machine learning analyses prioritized CVR-R_DB.Conclusions Lower CVR-R during deep breathing was associated with early oral semaglutide discontinuation due to nausea and/or vomiting. CVR-R_DB may support risk stratification at initiation.
SN - 2040-1116
SN - 2040-1124
ER -