Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial
Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vi...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Xiang Yan [verfasserIn] Xia Li [verfasserIn] Bingwen Liu [verfasserIn] Jiaqi Huang [verfasserIn] Yufei Xiang [verfasserIn] Yuhang Hu [verfasserIn] Xiaohan Tang [verfasserIn] Ziwei Zhang [verfasserIn] Gan Huang [verfasserIn] Zhiguo Xie [verfasserIn] Houde Zhou [verfasserIn] Zhenqi Liu [verfasserIn] Xiangbing Wang [verfasserIn] Richard David Leslie [verfasserIn] Zhiguang Zhou [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Übergeordnetes Werk: |
In: Signal Transduction and Targeted Therapy - Nature Publishing Group, 2016, 8(2023), 1, Seite 9 |
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| Übergeordnetes Werk: |
volume:8 ; year:2023 ; number:1 ; pages:9 |
| Links: |
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| DOI / URN: |
10.1038/s41392-023-01369-9 |
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| Katalog-ID: |
DOAJ08948956X |
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| 520 | |a Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). | ||
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10.1038/s41392-023-01369-9 doi (DE-627)DOAJ08948956X (DE-599)DOAJ09df3a80cbe14b24aec4eed0319c5852 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiang Yan verfasserin aut Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). Medicine R Biology (General) Xia Li verfasserin aut Bingwen Liu verfasserin aut Jiaqi Huang verfasserin aut Yufei Xiang verfasserin aut Yuhang Hu verfasserin aut Xiaohan Tang verfasserin aut Ziwei Zhang verfasserin aut Gan Huang verfasserin aut Zhiguo Xie verfasserin aut Houde Zhou verfasserin aut Zhenqi Liu verfasserin aut Xiangbing Wang verfasserin aut Richard David Leslie verfasserin aut Zhiguang Zhou verfasserin aut In Signal Transduction and Targeted Therapy Nature Publishing Group, 2016 8(2023), 1, Seite 9 (DE-627)881466581 (DE-600)2886872-9 20593635 nnns volume:8 year:2023 number:1 pages:9 https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/article/09df3a80cbe14b24aec4eed0319c5852 kostenfrei https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/toc/2059-3635 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2023 1 9 |
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10.1038/s41392-023-01369-9 doi (DE-627)DOAJ08948956X (DE-599)DOAJ09df3a80cbe14b24aec4eed0319c5852 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiang Yan verfasserin aut Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). Medicine R Biology (General) Xia Li verfasserin aut Bingwen Liu verfasserin aut Jiaqi Huang verfasserin aut Yufei Xiang verfasserin aut Yuhang Hu verfasserin aut Xiaohan Tang verfasserin aut Ziwei Zhang verfasserin aut Gan Huang verfasserin aut Zhiguo Xie verfasserin aut Houde Zhou verfasserin aut Zhenqi Liu verfasserin aut Xiangbing Wang verfasserin aut Richard David Leslie verfasserin aut Zhiguang Zhou verfasserin aut In Signal Transduction and Targeted Therapy Nature Publishing Group, 2016 8(2023), 1, Seite 9 (DE-627)881466581 (DE-600)2886872-9 20593635 nnns volume:8 year:2023 number:1 pages:9 https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/article/09df3a80cbe14b24aec4eed0319c5852 kostenfrei https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/toc/2059-3635 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2023 1 9 |
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10.1038/s41392-023-01369-9 doi (DE-627)DOAJ08948956X (DE-599)DOAJ09df3a80cbe14b24aec4eed0319c5852 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiang Yan verfasserin aut Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). Medicine R Biology (General) Xia Li verfasserin aut Bingwen Liu verfasserin aut Jiaqi Huang verfasserin aut Yufei Xiang verfasserin aut Yuhang Hu verfasserin aut Xiaohan Tang verfasserin aut Ziwei Zhang verfasserin aut Gan Huang verfasserin aut Zhiguo Xie verfasserin aut Houde Zhou verfasserin aut Zhenqi Liu verfasserin aut Xiangbing Wang verfasserin aut Richard David Leslie verfasserin aut Zhiguang Zhou verfasserin aut In Signal Transduction and Targeted Therapy Nature Publishing Group, 2016 8(2023), 1, Seite 9 (DE-627)881466581 (DE-600)2886872-9 20593635 nnns volume:8 year:2023 number:1 pages:9 https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/article/09df3a80cbe14b24aec4eed0319c5852 kostenfrei https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/toc/2059-3635 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2023 1 9 |
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10.1038/s41392-023-01369-9 doi (DE-627)DOAJ08948956X (DE-599)DOAJ09df3a80cbe14b24aec4eed0319c5852 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiang Yan verfasserin aut Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). Medicine R Biology (General) Xia Li verfasserin aut Bingwen Liu verfasserin aut Jiaqi Huang verfasserin aut Yufei Xiang verfasserin aut Yuhang Hu verfasserin aut Xiaohan Tang verfasserin aut Ziwei Zhang verfasserin aut Gan Huang verfasserin aut Zhiguo Xie verfasserin aut Houde Zhou verfasserin aut Zhenqi Liu verfasserin aut Xiangbing Wang verfasserin aut Richard David Leslie verfasserin aut Zhiguang Zhou verfasserin aut In Signal Transduction and Targeted Therapy Nature Publishing Group, 2016 8(2023), 1, Seite 9 (DE-627)881466581 (DE-600)2886872-9 20593635 nnns volume:8 year:2023 number:1 pages:9 https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/article/09df3a80cbe14b24aec4eed0319c5852 kostenfrei https://doi.org/10.1038/s41392-023-01369-9 kostenfrei https://doaj.org/toc/2059-3635 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2023 1 9 |
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combination therapy with saxagliptin and vitamin d for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial |
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Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial |
| abstract |
Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). |
| abstractGer |
Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). |
| abstract_unstemmed |
Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899). |
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Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial |
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Xia Li Bingwen Liu Jiaqi Huang Yufei Xiang Yuhang Hu Xiaohan Tang Ziwei Zhang Gan Huang Zhiguo Xie Houde Zhou Zhenqi Liu Xiangbing Wang Richard David Leslie Zhiguang Zhou |
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Xia Li Bingwen Liu Jiaqi Huang Yufei Xiang Yuhang Hu Xiaohan Tang Ziwei Zhang Gan Huang Zhiguo Xie Houde Zhou Zhenqi Liu Xiangbing Wang Richard David Leslie Zhiguang Zhou |
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