Shin Anna, Shin Ju-Young, Kang Eun Ha
Medical Research Collaboration Center, Seoul National University Bundang Hospital, Seongnam, Korea.
School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Diabetes Care. 2025 Feb 1;48(2):193-201. doi: 10.2337/dc24-1652.
We aim to compare the risk of nephrolithiasis among type 2 diabetes patients who initiated sodium-glucose cotransporter 2 inhibitors (SGLT2is) versus dipeptidyl peptidase 4 inhibitors (DPP4is), individually within stone never- and ever-formers.
Using the 2010-2021 Korea National Health Insurance Service database, we conducted a population-based cohort study, comparing initiators of SGLT2is versus DPP4is. The primary outcome was incident nephrolithiasis. Osteoarthritis encounters served as a negative control outcome. After 1:1 propensity score (PS) matching in stone never- and ever-formers, pooled and individual hazard ratios (HRs), incidence rate difference (IRD), and 95% CIs were reported. Subgroup analyses by sex, age, thiazide co-use, and baseline cardiovascular risk were done.
The 17,006 PS-matched pairs of SGLT2i and DPP4i initiators were pooled from stone never-formers (105,378 pairs) and ever-formers (11,628 pairs). Over a mean of 654 days, the risk of nephrolithiasis was lower in SGLT2i initiators than in DPP4i initiators: 0.65 vs. 1.12 events per 100 person-years, HR 0.54 (95% CI, 0.50-0.57), IRD -0.46 (95% CI, -0.21 to -0.52). Among never-formers, the HR was 0.43 (95% CI, 0.39-0.48) and IRD was -0.32 (95% CI, -0.27 to -0.36). Among ever-formers, the HR was 0.64 (95% CI, 0.59-0.69) and IRD was -2.26 (95% CI, -1.77 to -2.76). Near-null associations were found for osteoarthritis encounters. Results were consistent across subgroups.
We found a lower risk of nephrolithiasis associated with SGLT2is versus DPP4is in stone never- and ever-formers. Despite a greater relative risk reduction in the former, the absolute risk reduction was greater in the latter.
我们旨在比较起始使用钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）与二肽基肽酶4抑制剂（DPP4i）的2型糖尿病患者发生肾结石的风险，分别在从未患结石者和曾患结石者中进行比较。
利用2010 - 2021年韩国国民健康保险服务数据库，我们开展了一项基于人群的队列研究，比较SGLT2i起始使用者与DPP4i起始使用者。主要结局是新发肾结石。骨关节炎就诊作为阴性对照结局。在从未患结石者和曾患结石者中进行1:1倾向评分（PS）匹配后，报告汇总及个体风险比（HRs）、发病率差异（IRD）和95%置信区间（CIs）。按性别、年龄、噻嗪类药物联合使用情况及基线心血管风险进行亚组分析。
从从未患结石者（105,378对）和曾患结石者（11,628对）中汇总得到17,006对PS匹配的SGLT2i和DPP4i起始使用者。在平均654天的时间里，SGLT2i起始使用者发生肾结石的风险低于DPP4i起始使用者：每100人年分别为0.65例和1.12例事件，HR为0.54（95%CI，0.50 - 0.57），IRD为 - 0.46（95%CI， - 0.21至 - 0.52）。在从未患结石者中，HR为0.43（95%CI，0.39 - 0.48），IRD为 - 0.32（95%CI， - 0.27至 - 0.36）。在曾患结石者中，HR为0.64（95%CI，0.59 - 0.69），IRD为 - 2.26（95%CI， - 1.77至 - 2.76）。骨关节炎就诊的关联接近零。各亚组结果一致。
我们发现，在从未患结石者和曾患结石者中，与DPP4i相比，SGLT2i与较低的肾结石风险相关。尽管前者相对风险降低幅度更大，但后者的绝对风险降低幅度更大。
