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达格列净和达格列净-沙格列汀对 2 型糖尿病合并慢性肾脏病患者红细胞生成、铁和炎症标志物的影响:来自 DELIGHT 试验的数据。

Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial.

机构信息

Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.

Department of Nephrology and Laboratory Medicine, Kanazawa University, Ishikawa, Japan.

出版信息

Cardiovasc Diabetol. 2023 Nov 28;22(1):330. doi: 10.1186/s12933-023-02027-8.

Abstract

BACKGROUND

This post-hoc analysis of the DELIGHT trial assessed effects of the SGLT2 inhibitor dapagliflozin on iron metabolism and markers of inflammation.

METHODS

Patients with type 2 diabetes and albuminuria were randomized to dapagliflozin, dapagliflozin and saxagliptin, or placebo. We measured hemoglobin, iron markers (serum iron, transferrin saturation, and ferritin), plasma erythropoietin, and inflammatory markers (urinary MCP-1 and urinary/serum IL-6) at baseline and week 24.

RESULTS

360/461 (78.1%) participants had available biosamples. Dapagliflozin and dapagliflozin-saxagliptin, compared to placebo, increased hemoglobin by 5.7 g/L (95%CI 4.0, 7.3; p < 0.001) and 4.4 g/L (2.7, 6.0; p < 0.001) and reduced ferritin by 18.6% (8.7, 27.5; p < 0.001) and 18.4% (8.7, 27.1; p < 0.001), respectively. Dapagliflozin reduced urinary MCP-1/Cr by 29.0% (14.6, 41.0; p < 0.001) and urinary IL-6/Cr by 26.6% (9.1, 40.7; p = 0.005) with no changes in other markers.

CONCLUSIONS

Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02547935.

摘要

背景

这项 DELIGHT 试验的事后分析评估了 SGLT2 抑制剂达格列净对铁代谢和炎症标志物的影响。

方法

将患有 2 型糖尿病和白蛋白尿的患者随机分为达格列净组、达格列净-沙格列汀组和安慰剂组。我们在基线和 24 周时测量了血红蛋白、铁代谢标志物(血清铁、转铁蛋白饱和度和铁蛋白)、血浆促红细胞生成素和炎症标志物(尿单核细胞趋化蛋白-1 和尿/血清白细胞介素-6)。

结果

360/461(78.1%)名参与者有可用的生物样本。与安慰剂相比,达格列净和达格列净-沙格列汀分别使血红蛋白增加了 5.7 g/L(95%CI 4.0,7.3;p<0.001)和 4.4 g/L(2.7,6.0;p<0.001),铁蛋白降低了 18.6%(8.7,27.5;p<0.001)和 18.4%(8.7,27.1;p<0.001)。达格列净使尿 MCP-1/Cr 降低了 29.0%(14.6,41.0;p<0.001),尿 IL-6/Cr 降低了 26.6%(9.1,40.7;p=0.005),其他标志物无变化。

结论

达格列净增加了血红蛋白,降低了铁蛋白和尿炎症标志物,提示其对铁代谢和炎症可能有重要影响。

试验注册

ClinicalTrials.gov NCT02547935。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c32/10685512/04b8b66652ad/12933_2023_2027_Fig1_HTML.jpg

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