BACKGROUND AND HYPOTHESIS: Despite established cardiorenal benefits, concerns about urinary tract infection (UTI) risk may limit SGLT2 inhibitor use, especially in high-risk patients. 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.
METHODS: We conducted a post hoc analysis of individual-participant data from two randomized, double-blind, placebo-controlled trials of canagliflozin in type 2 diabetes. The primary outcome was time to first UTI; the secondary outcome was total UTI events, analyzed with Cox and Andersen-Gill models.
RESULTS: Among 8 614 participants, abnormal LE and nitrite were observed in 10.7% and 3.5%, respectively. After adjustment, the risk of first UTI increased with greater LE positivity (HRs: 1.72, 1.89, 2.77 for 1+, 2+, 3 + vs normal). Abnormal nitrite was also associated with higher risk (HR: 2.28 [1+], 1.66 [2+]). Similar findings were observed for total UTI events. Overall, canagliflozin did not increase risk of first (HR 1.06; 95% CI, 0.93-1.21) or total UTI events (HR 1.01; 0.86-1.18). LE and nitrite results did not significantly modify the effect of canagliflozin on the primary outcome. For LE, the hazard ratio (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 = 0.10). For nitrite, the HRs were 1.08 (0.94-1.24) and 0.92 (0.59-1.43), respectively (Pinteraction = 0.45). 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).
CONCLUSIONS: Although abnormal LE and nitrite were associated with increased UTI risk, canagliflozin did not further increase this risk in these subgroups. These findings do not support routine withholding of SGLT2 inhibitors in patients with dipstick findings suggestive of pyuria or bacteriuria.
| Discipline Area | Score |
|---|---|
| Endocrine |  |
| Nephrology |  |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
I’m not convinced by this study. It simply states, “Given the association between dipstick abnormalities and UTI risk...” This is exactly the claim I would question. At least in younger women, a dipstick test is not necessary to diagnose a UTI. We know that genital mycoses, in particular, are responsible for treatment discontinuation with SGLT-2 inhibitors. UTIs (which aren’t clearly defined clinically here) don’t play a clear role in this. Furthermore, canagliflozin is an SGLT-2 inhibitor with comparatively weak evidence supporting its benefits; I would never prescribe it.
This article demonstrates that the measurement of leukocyte esterase or nitrate is not useful in predicting urinary tract infections. They did a double blind controlled study of patients with UA‘s, and the findings of these indicators on a dipstick was not predictive of infections.
The clinically useful takeaway is probably not that dipstick abnormalities predict UTIs, which is expected, but that baseline pyuria or bacteruria did not appear to amplify UTI risk with canagliflozin. That said, the study still leaves open an important question: how clinically meaningful were these UTIs? In SGLT2 practice, genital mycoses are often more relevant than cystitis itself, and dipstick abnormalities may reflect colonization or asymptomatic inflammation rather than clinically significant infection. The paper is reassuring but perhaps more for prescribing behavior than for understanding infection biology.