Stopping sodium-glucose cotransporter-2 inhibitors following a urinary tract infection may not lower infection recurrence but could increase mortality, according to a recent study.

In a large population-based study, investigators found that new-onset urinary tract infections (UTI) among patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter (SGLT)-2 inhibitors was associated with higher cardiovascular and renal risks. The investigators demonstrated that patients who developed UTIs had a more than threefold increase in adverse cardiovascular events and mortality and a twofold increase in renal complications compared with those without infections. Further, discontinuation of SGLT-2 inhibitors following a UTI was linked to elevated risks of adverse cardiovascular and renal outcomes, with no observed reduction in recurrent UTIs.

Using data from the Hong Kong Hospital Authority’s Clinical Data Analysis and Reporting System, the investigators analyzed 61,606 adults with type 2 diabetes mellitus prescribed SGLT-2 inhibitors—empagliflozin, dapagliflozin, or canagliflozin—between January 2015 and June 2022. A total of 6.36% (n = 3,921) of the patients experienced at least one UTI during follow-up, of which 8.39% were severe. Patients with incident UTI were older (mean age = 68 vs 63 years); more likely to be female (50.78% vs 35.17% male); had longer duration of diabetes; and a higher prevalence of comorbidities such as chronic heart failure, cerebrovascular disease, and acute kidney injury.

Using target trial emulation with inverse probability weighting to minimize confounding, the investigators found that compared with patients without UTI, those who developed an infection were more than three times as likely to experience a major adverse cardiovascular event—including heart failure hospitalization, stroke, myocardial infarction, or all-cause mortality—and more than twice as likely to experience serious renal complications like a 50% decline in kidney function, end-stage renal failure, or mortality.

Following a UTI, 32.31% of patients discontinued SGLT-2 inhibitors. “These findings indicated that UTI is a substantial contributing factor to the discontinuation among SGLT-2 inhibitor users,” noted lead study author Mei-Zhen Wu, of the Division of Cardiology in the Department of Medicine at the University of Hong Kong–Shenzhen Hospital in China, and colleagues. Compared with patients who continued treatment, those who ceased SGLT-2 inhibitors after a UTI had about a one-third higher risk of adverse cardiovascular events and kidney complications as well as roughly a 40% and 50% higher risk of cardiovascular-related and all-cause mortality, respectively. The likelihood of developing another UTI, however, wasn't significantly different between the two groups.

The investigators reported no conflicts of interest.

Source: European Heart Journal