SGLT-2 inhibitors were not linked to severe or nonsevere UTIs vs DPP-4 inhibitors or GLP-1 agonists

An ACP Journal Club commentary called the results of this real-world, retrospective study reassuring regarding concerns about associations of urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

A study used a claims database to compare risk of urinary tract infections (UTIs) among patients initiating use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists. Results showed no significant differences between drug classes in UTIs requiring hospitalization or outpatient cases treated with antibiotics.

The study was published online July 30, 2019, and in the Aug. 20, 2019, issue of Annals of Internal Medicine. It was summarized in the August 2019 ACP Diabetes Monthly. The following commentary by Mayer B. Davidson, MD, was published in the ACP Journal Club section of the Dec. 17, 2019, Annals of Internal Medicine.

Given the mechanism of action of SGLT-2 inhibitors and that urinary glucose provides substrate for bacteria to grow, an increase in UTIs in patients receiving these agents could be expected. Although meta-analyses of randomized controlled trials of SGLT-2 inhibitors have reported conflicting results on UTIs, postmarketing reports of hospitalization for UTIs with sepsis or pyelonephritis prompted the U.S. Food and Drug Administration to issue a warning about severe UTIs. The real-world study by Dave and colleagues uses large databases and well-matched patients to compare severe and mild UTI outcomes ≤8 months after patients started new prescriptions for SGLT-2 inhibitors, DPP-4 inhibitors, or GLP-1 agonists. The results show that SGLT-2 inhibitors did not increase the risk for severe or nonsevere UTI outcomes compared with DPP-4 inhibitors or GLP-1 agonists.

Reports of an association between SGLT-2 inhibitors and UTIs in previous randomized controlled trials could have resulted from high scrutiny for UTIs under trial conditions, which may uncover more cases of asymptomatic bacteriuria. The current retrospective claims–based analysis may have case-finding and residual confounding limitations and can only demonstrate association—it is not designed to determine (or refute) causality. However, given the beneficial effects of SGLT-2 inhibitors on glycemia, blood pressure, weight, heart failure, cardiovascular disease, and renal function, it is reassuring that mild or severe UTIs are not increased with this class of drugs in a real-world setting.