Objective To emulate target trials comparing recurrence of nephrolithiasis among patients with pre-existing nephrolithiasis (overall and stratified by concomitant gout) initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus an active comparator. Design Target trial emulation studies. Setting Canadian population database, January 2014 to June 2022. Participants 20 146 patients with nephrolithiasis and type 2 diabetes, including those with concomitant gout at baseline, a high risk group. Interventions Initiation of an SGLT-2 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist, with a dipeptidyl peptidase-4 (DPP-4) inhibitor as alternative comparator. Main outcome measures The primary outcome was recurrent nephrolithiasis events ascertained from diagnoses during emergency department visits, hospital admissions, or outpatient visits. Secondary outcomes included nephrolithiasis resulting in hospital admission or emergency department visits and flare-up of gout, as well as a positive control outcome (genital infection) and negative control outcomes (osteoarthritis encounter and appendicitis). Poisson and Cox proportional hazards regression models were used (primary analyses), as well as overlap weighting. Results After inverse probability of treatment weighting, 1924 recurrent nephrolithiasis events occurred among the 14 456 weighted patients who used an SGLT-2 inhibitor (105.3 per 1000 person years), compared with 853 events among the 5877 weighted patients who used a GLP-1 receptor agonist (156.4 per 1000 person years). The adjusted rate ratio was 0.67 (95% confidence interval (CI) 0.57 to 0.79) and rate difference was −51 (95% CI −63 to −40) per 1000 person years, with a number needed to treat (NNT) of 20. Among those with recently active nephrolithiasis, the absolute rate difference was 219 per 1000 person years (NNT of 5). Protective associations persisted for nephrolithiasis events that required emergency department visits, hospital admissions, or procedures, and when an SGLT-2 inhibitor was compared with a DPP-4 inhibitor (rate ratio 0.73 (0.68 to 0.78), rate difference −38 (−46 to −29) per 1000 person years (NNT of 26)). Protective associations also persisted among patients with nephrolithiasis and concomitant gout, with a rate ratio of 0.67 (0.57 to 0.79) and rate difference of –53 (95% CI –78 to –27) per 1000 person years versus a GLP-1 receptor agonist (NNT of 19), and 0.63 (0.55 to 0.72) and–62 (–81 to –42) per 1000 person years, respectively, versus a DPP-4 inhibitor (NNT of 16). Furthermore, SGLT-2 inhibitor use was associated with a lower rate of gout flare-ups (rate ratio 0.72, 0.54 to 0.95, rate difference –16, –31 to –1 per 1000 person years) compared with GLP-1 receptor agonists (0.65, 0.52 to 0.82, and –21, –33 to –9 per 1000 person years) compared with DPP-4 inhibitors. SGLT-2 inhibitor initiators showed higher risk of genital infection (eg, hazard ratio 2.21, 95% CI 1.68 to 2.90, and rate difference 13 per 1000 person years), but no altered risk of osteoarthritis encounter (0.87, 0.68 to 1.1, and –2 per 1000 person years) or appendicitis (1.07, 0.69 to 1.67, and 1 per 1000 person years). Results were similar when propensity score overlap weighting was applied. Conclusions The benefits associated with SGLT-2 inhibitor for patients with nephrolithiasis in these target trial emulations suggest they may be a useful addition to current treatments to simultaneously manage nephrolithiasis recurrence and comorbidities, including gout. Data for this study are not publicly available because of a data use agreement. For requests to access the study data, contact the corresponding author. Access to data provided by the data stewards is subject to approval but can be requested for research projects through the data stewards or their designated service providers. More information on the datasets used in this study are available at the PopData project webpage ([https://my.popdata.bc.ca/project\_listings/21-048/collection\_approval_dates][1]). All inferences, opinions, and conclusions drawn in this publication are those of the author(s), and do not reflect the opinions or policies of the data steward(s). [1]: https://my.popdata.bc.ca/project_listings/21-048/collection_approval_dates

中文翻译：

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钠-葡萄糖协同转运蛋白-2 抑制剂对已有肾结石或痛风患者复发性肾结石的疗效比较：靶向试验模拟研究


目的 模拟目标试验，比较开始使用钠-葡萄糖协同转运蛋白 2 （SGLT-2） 抑制剂的既往肾结石患者 （总体和伴随痛风分层） 肾结石复发与活性对照剂。设计 Target 试验仿真研究。设置 2014 年 1 月至 2022 年 6 月的加拿大人口数据库。参与者 20 146 名肾结石和 2 型糖尿病患者，包括基线时伴有痛风的患者，这是一个高危人群。干预措施 开始使用 SGLT-2 抑制剂或胰高血糖素样肽-1 （GLP-1） 受体激动剂，以二肽基肽酶-4 （DPP-4） 抑制剂作为替代对照。主要结局指标 主要结局是从急诊科就诊、住院或门诊就诊期间的诊断中确定的复发性肾结石事件。次要结局包括肾结石导致入院或急诊科就诊和痛风发作，以及阳性对照结局（生殖器感染）和阴性对照结局（骨关节炎发作和阑尾炎）。使用 Poisson 和 Cox 比例风险回归模型 （主要分析） 以及重叠加权。结果 在治疗加权的逆概率后，使用 SGLT-2 抑制剂的 14 456 例加权患者中发生了 1924 例复发性肾结石事件 （105.3例/1000 人年），而使用 GLP-1 受体激动剂的 5877 例加权患者中发生了 853 例事件 （156.4例/1000 人年）。调整后的比率为 0.67 （95% 置信区间 （CI） 0.57 至 0.79），比率差异为每 1000 人年 -51 （95% CI -63 至 -40），需治疗人数 （NNT） 为 20。 在近期活动性肾结石患者中，绝对发生率差异为 219/1000 人年 （NNT 为 5）。对于需要急诊科就诊、住院或手术的肾结石事件，以及将 SGLT-2 抑制剂与 DPP-4 抑制剂进行比较时（率比 0.73 （0.68 至 0.78），率差 -38 （-46 至 -29） /1000 人年 （NNT 为 26））时，保护性关联仍然存在。保护性关联在肾结石合并痛风患者中也持续存在，与 GLP-1 受体激动剂（NNT 为 19）相比，每 1000 人年的比率比为 0.67（0.57 至 0.79），率差为 -53（95% CI -78 至 -27），每 1000 人年 0.63（0.55 至 0.72）和 -62（-81 至 -42）。 分别与 DPP-4 抑制剂 （NNT 为 16） 相比。此外，与 DPP-4 抑制剂相比，与 GLP-1 受体激动剂 （0.65、0.52 至 0.82 和 -21、-33 至 -9/1000 人年） 相比，使用 SGLT-2 抑制剂与较低的痛风发作率 （比率比 0.72、0.54 至 0.95，率差 -16、-31 至 -1/1000 人年） 相关。SGLT-2抑制剂引发剂显示生殖器感染的风险较高（例如，风险比 2.21,95% CI 1.68 至 2.90，率差 13/1000 人年），但骨关节炎发生风险没有改变（0.87、0.68 至 1.1 和 -2/1000 人年）或阑尾炎（1.07、0.69 至 1.67 和 1/1000 人年）。当应用倾向得分重叠加权时，结果相似。结论在这些目标试验模拟中，SGLT-2 抑制剂对肾结石患者相关的益处表明，它们可能是当前治疗的有用补充，可同时控制肾结石复发和合并症，包括痛风。 由于数据使用协议，本研究的数据不公开。有关访问研究数据的请求，请联系相应作者。访问数据管理员提供的数据需要获得批准，但可以通过数据管理员或其指定的服务提供商为研究项目请求。有关本研究中使用的数据集的更多信息，请访问 PopData 项目网页 （[https://my.popdata.bc.ca/project\_listings/21-048/collection\_approval_dates][1]）。本出版物中得出的所有推论、意见和结论均为作者的观点、意见和结论，不反映数据管家的观点或政策。[1]：https://my.popdata.bc。编号：ca/project_listings/21-048/collection_approval_dates