Fishkin Alisa, Rozenberg Aliza, Schechter Meir, Sehtman-Shachar Dvora R, Aharon-Hananel Genya, Leibowitz Gil, Yanuv Ilan, Mosenzon Ofri
Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.
Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Diabetes Metab Res Rev. 2025 Jul;41(5):e70066. doi: 10.1002/dmrr.70066.
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.
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.
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.
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.
随机安慰剂对照临床试验表明，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，在慢性肾脏病患者中尤为显著。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且与活性对照相比的更广泛T2D患者群体。我们总结了起始使用GLP-1 RA的T2D患者与其他降糖药物相比发生不良肾脏结局的真实世界数据。
我们检索了PubMed和Embase数据库中的观察性队列研究（2005年4月至2025年1月；PROSPERO注册号CRD42023405356）。将起始使用GLP-1 RA的患者与钠-葡萄糖协同转运蛋白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比较。结局包括蛋白尿进展风险、估算肾小球滤过率（eGFR）较基线降低≥40%或≥50%、急性肾损伤（AKI）、肾脏相关住院以及终末期肾病（ESKD），具体取决于数据的可获得性。我们在随机效应模型中使用对数风险比（HR）的逆方差加权平均值来综合数据。
31项研究符合条件，涵盖1,601,389例患者（平均年龄49 - 78岁，女性占5% - 64%），其中分别有21项、6项、5项和1项研究使用SGLT2i、DPP4i、基础胰岛素和磺脲类药物作为对照。与SGLT2i相比，起始使用GLP-1 RA的患者发生AKI的风险更高（HR [95% CI] 1.12 [1.05 - 1.20]）、肾脏相关住院风险更高（1.66 [1.01 - 2.73]）以及eGFR降低≥40%的风险更高（1.40 [1.27 - 1.53]），但在eGFR降低≥50%或ESKD的风险方面没有差异证据。与DPP4i相比，起始使用GLP-1 RA的患者发生eGFR降低≥50%的风险更低（0.84 [0.76 - 0.92]）、肾脏相关住院风险更低（0.73 [0.65 - 0.83]）以及ESKD风险更低（0.70 [0.63 - 0.78]）。在将GLP-1 RA与磺脲类药物比较时也观察到了类似的益处。与基础胰岛素相比，起始使用GLP-1 RA与蛋白尿进展风险较低相关（0.89 [0.80 - 0.99]），关于降低ESKD风险的潜在益处的数据不一致。
在T2D患者中，在现实环境中起始使用GLP-1 RA与DPP4i、磺脲类药物和基础胰岛素相比可能与更好的肾脏结局相关，而与SGLT2i相比肾脏结局更差。
