SGLT2 inhibitors and urinary tract infections: resolving the dilemma through aetiological classification

This commentary refers to ‘Stakeholder meeting report for ENHANCE CVH: a trial to improve maternal and child cardiovascular health in Nigeria’, by C. N. O. Nartey et al., https://doi.org/10.1093/eurheartj/ehaf288 and the discussion piece ‘Revisiting the Link Between SGLT2 Inhibitors and Urinary Tract Infections’, by M. Z. Wu et al., https://doi.org/10.1093/eurheartj/ehaf788. The association between sodium–glucose cotransporter-2 (SGLT2) inhibitors and urinary tract infections (UTIs) remains a subject of ongoing controversy. Theoretically, glycosuria provides a fertile medium for bacterial growth, a concern reinforced by US Food and Drug Administration (FDA) safety communications warning of serious UTI and subsequent label modifications.1 Consequently, discontinuing SGLT2 inhibitors after an incident UTI has become a popular, albeit conservative, practice among clinicians.2 In this context, the study by Wu et al. is valuable as it challenges this conservative practice by demonstrating that discontinuation significantly worsens cardiovascular and renal outcomes.2 The authors also reported that discontinuation did not reduce the risk of recurrent UTI [hazard ratio (HR) 0.96]. However, given the acknowledged violation of the proportional hazards assumption, a single summary HR is potentially misleading. Visualizing the time-varying risk would have allowed for a more robust interpretation.