Urinary dipstick findings and UTI risk with SGLT2 inhibitors: a post-hoc analysis of the CANVAS and CREDENCE trials.

We hypothesized that urine leukocyte esterase (LE) and nitrite-findings compatible with pyuria or bacteriuria-predict subsequent UTI risk and modify the association between canagliflozin and UTIs.

我们假设尿液中的白细胞酯酶（LE）和亚硝酸盐-与脓尿或细菌尿相符的发现-可以预测随后的UTI风险，并改变canagliflozin与UTIs之间的关联。

Methods

We conducted a post-hoc analysis of individual-participant data from two randomized, double-blind, placebo-controlledtrials of canagliflozin in type 2 diabetes.

我们对两项随机、双盲、安慰剂对照试验中canagliflozin治疗2型糖尿病的个体参与者数据进行了事后分析。

The primary outcome was time to first UTI; the secondary outcome was total UTI events, analyzed with Cox and Andersen-Gill models.

主要结果是首次UTI发生的时间；次要结果是总UTI事件，使用Cox和Andersen-Gill模型进行分析。

Results

Among 8614 participants, abnormal LE and nitrite were observed in 10.7% and 3.5%, respectively.

在8614名参与者中，观察到异常LE和亚硝酸盐的分别占10.7%和3.5%。

After adjustment, the risk of first UTI increased with greater LE positivity [hazard ratio(HR) 1.72, 1.92, 2.81 for 1+, 2+, 3+ vs normal].

调整后，首次UTI的风险随着LE阳性程度的增加而增加[风险比（HR）分别为1.72（1+），1.92（2+），2.81（3+）与正常相比]。

Abnormal nitrite was also associated with higher risk [HR 2.28 (1+), 1.66 (2+)].

异常亚硝酸盐也与更高的风险相关[HR分别为2.28（1+），1.66（2+）]。

Similar findings were observed for total UTI events.

对于总UTI事件也观察到了类似的结果。

Overall, canagliflozin did not increase risk of first [HR 1.07; 95% confidence interval(CI) 0.93-1.22] or total UTI events (HR 1.01; 95% CI 0.86-1.17).

总体而言，卡格列净并未增加首次尿路感染事件的风险（HR 1.07; 95%置信区间（CI）0.93-1.22）或总的尿路感染事件（HR 1.01; 95% CI 0.86-1.17）。

LE and nitrite results did not significantly modify the effect of canagliflozin on the primary outcome.

对于白细胞酯酶（LE）和亚硝酸盐结果，并未显著改变卡格列净对主要结果的影响。

For LE, the HR for first UTI was 1.17 (95% CI 1.00-1.38) in the normal group and 0.94 (0.73-1.21) in the abnormal group (Pinteraction = .10).

对于LE，正常组首次尿路感染的HR为1.17（95% CI 1.00-1.38），异常组为0.94（0.73-1.21）（Pinteraction = .10）。

For nitrite, the HRs were 1.08 (0.94-1.24) and 0.92 (0.59-1.43), respectively (Pinteraction = .45).

对于亚硝酸盐，HR分别为1.08（0.94-1.24）和0.92（0.59-1.43）（Pinteraction = .45）。

For the secondary outcome, canagliflozin also did not increase the risk of total UTI events in either the abnormal LE or nitrite group [HR 0.76 (0.58-0.99) and 1.18 (0.79-1.76), respectively].

对于次要结果，卡格列净也并未增加异常LE或亚硝酸盐组总的尿路感染事件风险[HR分别为0.76（0.58-0.99）和1.18（0.79-1.76）]。

Conclusions

Although abnormal LE and nitrite were associated with increased UTI risk, canagliflozin did not further increase this risk in these subgroups.

尽管异常LE和亚硝酸盐与增加的尿路感染风险相关，但卡格列净并未在这些亚组中进一步增加这一风险。

These findings do not support routine withholding of SGLT2i in patients with dipstick findings suggestive of pyuria or bacteriuria.

这些发现不支持在有试纸检测提示脓尿或细菌尿的患者中常规停用SGLT2i。