Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study

Abstract Background To compare the effects of switching from dipeptidyl peptidase 4 (DPP-4) inhibitors to oral semaglutide on oxidative stress and glucose variability assessed by continuous glucose monitoring in patients with type 2 diabetes mellitus (T2DM). Methods This was an open-label, prospecti...

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Main Authors: Makoto Ohara, Hiroki Yokoyama, Hiroaki Seino, Tomoki Fujikawa, Yo Kohata, Noriyuki Takahashi, Shunichiro Irie, Michishige Terasaki, Yusaku Mori, Tomoyasu Fukui, Sho-ichi Yamagishi
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Diabetology & Metabolic Syndrome
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Online Access:https://doi.org/10.1186/s13098-025-01691-y
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author Makoto Ohara
Hiroki Yokoyama
Hiroaki Seino
Tomoki Fujikawa
Yo Kohata
Noriyuki Takahashi
Shunichiro Irie
Michishige Terasaki
Yusaku Mori
Tomoyasu Fukui
Sho-ichi Yamagishi
author_facet Makoto Ohara
Hiroki Yokoyama
Hiroaki Seino
Tomoki Fujikawa
Yo Kohata
Noriyuki Takahashi
Shunichiro Irie
Michishige Terasaki
Yusaku Mori
Tomoyasu Fukui
Sho-ichi Yamagishi
author_sort Makoto Ohara
collection DOAJ
description Abstract Background To compare the effects of switching from dipeptidyl peptidase 4 (DPP-4) inhibitors to oral semaglutide on oxidative stress and glucose variability assessed by continuous glucose monitoring in patients with type 2 diabetes mellitus (T2DM). Methods This was an open-label, prospective, randomized, multicenter, parallel-group comparison study conducted over 24 weeks. Patients with T2DM who had been taking regular doses of DPP-4 inhibitors for at least 12 weeks were enrolled. They were randomly assigned to either continue on DPP-4 inhibitors (DPP-4 inhibitor group) or switch to oral semaglutide at 3 mg/day, with a dose increase to 7 mg/day after 4 weeks (semaglutide group). The primary endpoint was the change in the diacron-reactive oxygen metabolites test, an oxidative stress marker. Secondary endpoints included changes in glucose variability assessed using continuous glucose monitoring, metabolic indices, physical assessments, and Diabetes Treatment Satisfaction Questionnaire scores. Results Fifty-eight patients with T2DM were randomized to the semaglutide group (n = 30) and the DPP-4 inhibitor group (n = 28). Six patients in the semaglutide group and one patient in the DPP-4 inhibitor group dropped out during the study. Ultimately, data from 24 patients in the semaglutide group and 27 patients in the DPP-4 inhibitor group were included for analysis. Switching to oral semaglutide therapy for 24 weeks significantly reduced oxidative stress, glucose variability, and hemoglobin A1c levels compared to continuous treatment with DPP-4 inhibitors. However, there was no significant difference in Diabetes Treatment Satisfaction Questionnaire scores between the two groups. (II) Conclusions Our study demonstrated that switching to oral semaglutide therapy from DPP-4 inhibitors significantly improved oxidative stress and glycemic parameters, including glucose variability, in patients with T2DM. Trial registration: jRCT1031210620.
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series Diabetology & Metabolic Syndrome
spelling doaj-art-51d2e499a4f34e85adf439664f85d5e92025-08-20T03:18:39ZengBMCDiabetology & Metabolic Syndrome1758-59962025-04-0117111310.1186/s13098-025-01691-yEffects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison studyMakoto Ohara0Hiroki Yokoyama1Hiroaki Seino2Tomoki Fujikawa3Yo Kohata4Noriyuki Takahashi5Shunichiro Irie6Michishige Terasaki7Yusaku Mori8Tomoyasu Fukui9Sho-ichi Yamagishi10Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineDepartment of Internal Medicine, Jiyugaoka Medical ClinicDepartment of Internal Medicine, Seino Internal Medicine ClinicDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineDepartment of Internal Medicine, Tokatsu HospitalDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineDivision of Diabetes, Metabolism, and Endocrinology, Antiglycation Research Section, Department of Medicine, Showa University Graduate School of MedicineDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University Graduate School of MedicineAbstract Background To compare the effects of switching from dipeptidyl peptidase 4 (DPP-4) inhibitors to oral semaglutide on oxidative stress and glucose variability assessed by continuous glucose monitoring in patients with type 2 diabetes mellitus (T2DM). Methods This was an open-label, prospective, randomized, multicenter, parallel-group comparison study conducted over 24 weeks. Patients with T2DM who had been taking regular doses of DPP-4 inhibitors for at least 12 weeks were enrolled. They were randomly assigned to either continue on DPP-4 inhibitors (DPP-4 inhibitor group) or switch to oral semaglutide at 3 mg/day, with a dose increase to 7 mg/day after 4 weeks (semaglutide group). The primary endpoint was the change in the diacron-reactive oxygen metabolites test, an oxidative stress marker. Secondary endpoints included changes in glucose variability assessed using continuous glucose monitoring, metabolic indices, physical assessments, and Diabetes Treatment Satisfaction Questionnaire scores. Results Fifty-eight patients with T2DM were randomized to the semaglutide group (n = 30) and the DPP-4 inhibitor group (n = 28). Six patients in the semaglutide group and one patient in the DPP-4 inhibitor group dropped out during the study. Ultimately, data from 24 patients in the semaglutide group and 27 patients in the DPP-4 inhibitor group were included for analysis. Switching to oral semaglutide therapy for 24 weeks significantly reduced oxidative stress, glucose variability, and hemoglobin A1c levels compared to continuous treatment with DPP-4 inhibitors. However, there was no significant difference in Diabetes Treatment Satisfaction Questionnaire scores between the two groups. (II) Conclusions Our study demonstrated that switching to oral semaglutide therapy from DPP-4 inhibitors significantly improved oxidative stress and glycemic parameters, including glucose variability, in patients with T2DM. Trial registration: jRCT1031210620.https://doi.org/10.1186/s13098-025-01691-yContinuous glucose monitoringGlucose variabilityOxidative stressType 2 diabetes mellitusGlucagon-like peptide-1 receptor agonistsDipeptidyl peptidase 4 inhibitor
spellingShingle Makoto Ohara
Hiroki Yokoyama
Hiroaki Seino
Tomoki Fujikawa
Yo Kohata
Noriyuki Takahashi
Shunichiro Irie
Michishige Terasaki
Yusaku Mori
Tomoyasu Fukui
Sho-ichi Yamagishi
Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study
Diabetology & Metabolic Syndrome
Continuous glucose monitoring
Glucose variability
Oxidative stress
Type 2 diabetes mellitus
Glucagon-like peptide-1 receptor agonists
Dipeptidyl peptidase 4 inhibitor
title Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study
title_full Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study
title_fullStr Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study
title_full_unstemmed Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study
title_short Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study
title_sort effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes an open label prospective randomized multicenter parallel group comparison study
topic Continuous glucose monitoring
Glucose variability
Oxidative stress
Type 2 diabetes mellitus
Glucagon-like peptide-1 receptor agonists
Dipeptidyl peptidase 4 inhibitor
url https://doi.org/10.1186/s13098-025-01691-y
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