Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists Versus Other Glucose-Lowering Agents in People With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Data

IF 6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes/Metabolism Research and Reviews Pub Date : 2025-07-23 DOI:10.1002/dmrr.70066

Alisa Fishkin, Aliza Rozenberg, Meir Schechter, Dvora R. Sehtman-Shachar, Genya Aharon-Hananel, Gil Leibowitz, Ilan Yanuv, Ofri Mosenzon

{"title":"Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists Versus Other Glucose-Lowering Agents in People With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Data","authors":"Alisa Fishkin, Aliza Rozenberg, Meir Schechter, Dvora R. Sehtman-Shachar, Genya Aharon-Hananel, Gil Leibowitz, Ilan Yanuv, Ofri Mosenzon","doi":"10.1002/dmrr.70066","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>We searched PubMed and Embase for observational cohort studies (April 2005–January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49–78 years, 5%–64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05–1.20]), kidney-related hospitalizations (1.66 [1.01–2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27–1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76–0.92]), kidney-related hospitalizations (0.73 [0.65–0.83]), and ESKD (0.70 [0.63–0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80–0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.</p>\n </section>\n </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 5","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70066","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes/Metabolism Research and Reviews","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/dmrr.70066","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents.

Materials and Methods

We searched PubMed and Embase for observational cohort studies (April 2005–January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.

Results

Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49–78 years, 5%–64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05–1.20]), kidney-related hospitalizations (1.66 [1.01–2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27–1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76–0.92]), kidney-related hospitalizations (0.73 [0.65–0.83]), and ESKD (0.70 [0.63–0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80–0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.

Conclusions

In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.

Abstract Image

查看原文本刊更多论文

2型糖尿病患者使用胰高血糖素样肽-1受体激动剂与其他降糖药的肾脏结局：对真实世界数据的系统回顾和荟萃分析

随机安慰剂对照临床试验显示，胰高血糖素样肽-1受体激动剂（GLP-1 RA）可降低2型糖尿病（T2D）患者的肾脏风险，尤其是慢性肾病患者。目前尚不清楚这些发现是否适用于在现实环境中接受治疗的更广泛的T2D患者，并与积极对照进行比较。我们总结了t2dm患者启动GLP-1 RA与其他降糖药的不良肾脏结局的真实数据。我们检索了PubMed和Embase的观察性队列研究(2005年4月- 2025年1月；普洛斯彼罗CRD42023405356)。GLP-1 RA的启动剂与钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）、二肽基肽酶4抑制剂（DPP4i）、磺脲类药物或基础胰岛素进行了比较。结果包括蛋白尿进展、eGFR较基线降低≥40%或≥50%、急性肾损伤（AKI）、肾脏相关住院和终末期肾病（ESKD）的风险。我们使用随机效应模型中对数风险比（HR）s的逆方差加权平均来综合数据。31项研究符合条件，包括1,601,389例患者（平均年龄49-78岁，5%-64%为女性），其中分别有21例、6例、5例和1例使用SGLT2i、DPP4i、基础胰岛素和磺脲类药物作为比较物。与SGLT2i相比，GLP-1 RA启动者发生AKI （HR [95% CI] 1.12[1.05-1.20]）、肾脏相关住院（1.66[1.01-2.73]）和eGFR降低≥40%（1.40[1.27-1.53]）的风险更高，但没有证据表明eGFR降低≥50%或ESKD的风险存在差异。与DPP4i相比，GLP-1 RA启动剂发生eGFR降低≥50%（0.84[0.76-0.92]）、肾脏相关住院（0.73[0.65-0.83]）和ESKD（0.70[0.63-0.78]）的风险较低。当GLP-1 RA与磺脲类药物进行比较时，也观察到类似的益处。与基础胰岛素相比，GLP-1 RA起始与蛋白尿进展风险较低相关（0.89[0.80-0.99]），关于降低ESKD风险的可能益处的数据不一致。结论：在t2dm患者中，与DPP4i、磺脲类药物和基础胰岛素相比，现实环境中GLP-1 RA的启动可能与肾脏预后改善有关，与SGLT2i相比，肾脏预后更差。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes/Metabolism Research and Reviews 医学-内分泌学与代谢

CiteScore

17.20

自引率

2.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.