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The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated th...

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Autores principales: Kitao, Naoyuki, Miyoshi, Hideaki, Furumoto, Tomoo, Ono, Kota, Nomoto, Hiroshi, Miya, Aika, Yamamoto, Chiho, Inoue, Atsushi, Tsuchida, Kenichi, Manda, Naoki, Kurihara, Yoshio, Aoki, Shin, Nakamura, Akinobu, Atsumi, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634845/
https://www.ncbi.nlm.nih.gov/pubmed/29017497
http://dx.doi.org/10.1186/s12933-017-0607-6
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author Kitao, Naoyuki
Miyoshi, Hideaki
Furumoto, Tomoo
Ono, Kota
Nomoto, Hiroshi
Miya, Aika
Yamamoto, Chiho
Inoue, Atsushi
Tsuchida, Kenichi
Manda, Naoki
Kurihara, Yoshio
Aoki, Shin
Nakamura, Akinobu
Atsumi, Tatsuya
author_facet Kitao, Naoyuki
Miyoshi, Hideaki
Furumoto, Tomoo
Ono, Kota
Nomoto, Hiroshi
Miya, Aika
Yamamoto, Chiho
Inoue, Atsushi
Tsuchida, Kenichi
Manda, Naoki
Kurihara, Yoshio
Aoki, Shin
Nakamura, Akinobu
Atsumi, Tatsuya
author_sort Kitao, Naoyuki
collection PubMed
description BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin. METHODS: In this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500–750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed. RESULTS: Ninety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m(2); HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (− 0.80 ± 0.38% vs. − 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (− 0.51 [− 1.08–0.06]% vs. − 0.58 [− 1.20–0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66–0.62; p < 0.01), the change did not differ significantly between the two groups (− 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01). CONCLUSIONS: Regardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-017-0607-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-56348452017-10-19 The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3) Kitao, Naoyuki Miyoshi, Hideaki Furumoto, Tomoo Ono, Kota Nomoto, Hiroshi Miya, Aika Yamamoto, Chiho Inoue, Atsushi Tsuchida, Kenichi Manda, Naoki Kurihara, Yoshio Aoki, Shin Nakamura, Akinobu Atsumi, Tatsuya Cardiovasc Diabetol Original Investigation BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin. METHODS: In this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500–750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed. RESULTS: Ninety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m(2); HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (− 0.80 ± 0.38% vs. − 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (− 0.51 [− 1.08–0.06]% vs. − 0.58 [− 1.20–0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66–0.62; p < 0.01), the change did not differ significantly between the two groups (− 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01). CONCLUSIONS: Regardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-017-0607-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-10 /pmc/articles/PMC5634845/ /pubmed/29017497 http://dx.doi.org/10.1186/s12933-017-0607-6 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Kitao, Naoyuki
Miyoshi, Hideaki
Furumoto, Tomoo
Ono, Kota
Nomoto, Hiroshi
Miya, Aika
Yamamoto, Chiho
Inoue, Atsushi
Tsuchida, Kenichi
Manda, Naoki
Kurihara, Yoshio
Aoki, Shin
Nakamura, Akinobu
Atsumi, Tatsuya
The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)
title The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)
title_full The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)
title_fullStr The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)
title_full_unstemmed The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)
title_short The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)
title_sort effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (sapporo athero-incretin study 3)
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634845/
https://www.ncbi.nlm.nih.gov/pubmed/29017497
http://dx.doi.org/10.1186/s12933-017-0607-6
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