与二肽基肽酶-4抑制剂相比，钠-葡萄糖协同转运蛋白-2抑制剂对老年2型糖尿病患者肾结石的异质性影响。 - Suppr | 超能文献

BACKGROUND

Type 2 diabetes (T2D) is associated with an increased risk of nephrolithiasis. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2i) may reduce this risk; however, data remain inconclusive.

OBJECTIVE

To examine the risk of nephrolithiasis among users of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i) in a real-world population of older adults with T2D.

METHODS

A retrospective cohort study was conducted using claims data from a sample of national Medicare beneficiaries. Individuals with T2D who initiated SGLT2i or DPP4i therapy between January 1, 2016, and December 31, 2018, were identified. The index date was defined as the date of the first prescription for either SGLT2i or DPP4i, with no prior use of either drug in the preceding year. Patients were followed from the index date until the earliest occurrence of a medical encounter with a primary diagnosis of nephrolithiasis, death, or December 31, 2018. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates, including sociodemographic characteristics, comorbidities, and comedication use. Cox proportional hazards regression models were applied to compare the risk of nephrolithiasis between SGLT2i and DPP4i users. Additional analyses were conducted within subgroups defined by sex, race, and baseline nephrolithiasis status.

RESULTS

Of 116,506 included Medicare beneficiaries with T2D (mean age 72 ± 10 years, 53% women), 0.96% developed nephrolithiasis over a median follow-up of 360 days (interquartile range [IQR] 200-467 days). The incidence rate of nephrolithiasis was 9.89 (95% confidence interval [CI] 8.49-11.52) and 11.02 (95% CI 10.34-11.73) events per 1000 person-years in the SGLT2i and DPP4i groups, respectively. After applying IPTW, baseline characteristics were well balanced between the two groups. SGLT2i use was associated with a significantly lower risk of nephrolithiasis compared to DPP4i use (hazard ratio [HR], 0.81; 95% CI 0.66-0.99; p = 0.04). In subgroup analyses, SGLT2i use compared to DPP4i was associated with a significantly lower risk of nephrolithiasis among males (HR 0.75; 95% CI 0.58-0.98; p = 0.04), non-Hispanic Black (NHB) individuals (HR 0.22; 95% CI 0.07-0.64; p < 0.01), and those without baseline nephrolithiasis (HR 0.68; 95% CI 0.53-0.88; p < 0.01).

CONCLUSIONS

In older adults with T2D, SGLT2i use was associated with a lower risk of nephrolithiasis compared to DPP4i, particularly among men, NHB individuals, and those without baseline nephrolithiasis. Although causality cannot be established, these findings provide real-world evidence supporting a potential benefit of SGLT2is in reducing nephrolithiasis risk, offering valuable insights to guide the selection of glucose-lowering drugs in older adults with T2D.

摘要

背景

2型糖尿病（T2D）与肾结石风险增加相关。新出现的证据表明，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可能会降低这种风险；然而，数据仍不明确。

目的

在患有T2D的老年真实人群中，研究与二肽基肽酶-4抑制剂（DPP4i）相比，SGLT2i使用者发生肾结石的风险。

方法

使用来自全国医疗保险受益人的样本理赔数据进行一项回顾性队列研究。确定2016年1月1日至2018年12月31日期间开始使用SGLT2i或DPP4i治疗的T2D患者。索引日期定义为首次开具SGLT2i或DPP4i处方的日期，前一年未使用过这两种药物。从索引日期开始对患者进行随访，直至最早出现主要诊断为肾结石的医疗接触、死亡或2018年12月31日。使用治疗权重的逆概率（IPTW）来平衡基线协变量，包括社会人口学特征、合并症和联合用药情况。应用Cox比例风险回归模型比较SGLT2i和DPP4i使用者之间肾结石的风险。在按性别、种族和基线肾结石状态定义的亚组中进行了额外分析。

结果

在纳入的116,506名患有T2D的医疗保险受益人中（平均年龄72±10岁，53%为女性），在中位随访360天（四分位间距[IQR]200 - 467天）期间，0.96%发生了肾结石。SGLT2i组和DPP4i组每1000人年的肾结石发病率分别为9.89（95%置信区间[CI]8.49 - 11.52）和11.02（95%CI 10.34 - 11.73）例。应用IPTW后，两组之间的基线特征得到了很好的平衡。与使用DPP4i相比，使用SGLT2i与肾结石风险显著降低相关（风险比[HR]，0.81；95%CI 0.66 - 0.99；p = 0.04）。在亚组分析中，与使用DPP4i相比，在男性（HR 0.75；95%CI 0.58 - 0.98；p = 0.04）、非西班牙裔黑人（NHB）个体（HR 0.22；95%CI 0.07 - 0.64；p < 0.01）以及无基线肾结石的个体（HR 0.68；95%CI 0.53 - 0.88；p < 0.01）中，使用SGLT2i与肾结石风险显著降低相关。

结论

在患有T2D的老年人中，与DPP4i相比，使用SGLT2i与较低的肾结石风险相关，尤其是在男性、NHB个体以及无基线肾结石的个体中。尽管无法确定因果关系，但这些发现提供了真实世界的证据，支持SGLT2i在降低肾结石风险方面的潜在益处，为指导患有T2D的老年人选择降糖药物提供了有价值的见解。