SGLT2 inhibitors and infection risk in patients with type 2 diabetes

Compared with the general population, individuals with diabetes have a higher risk of developing infections such as foot infections, respiratory tract infections, urinary tract infections, sepsis and postoperative infection.Although systematic reviews of randomized controlled trials have consistently shown an increased risk of genital infections with sodium–glucose cotransporter 2 (SGLT2) inhibitors, emerging evidence suggests that SGLT2 inhibitors have pleiotropic effects that may protect against certain infections. To further examine this issue, researchers in Australia systematically reviewed real-world evidence from observational studies on the association between SGLT2 inhibitors and infections among adults with type 2 diabetes.The authors contend that evidence from observational studies is important, as many randomized controlled trials of SGLT2 inhibitors excluded patients with a history of infections, had relatively small sample sizes, and an average follow-up of only 42 weeks. Well-conducted observational studies can provide valuable evidence on long-term, patient-centred outcomes not routinely assessed in randomized controlled trials. The investigators searched published literature from 2012–2024 for observational studies conducted in adults with type 2 diabetes. The analysis compared exposure to SGLT2 inhibitors with nonusers or users of other glucose-lowering medications. Studies reporting outcome estimates for specific nongenitourinary infections were included. Key results:The investigators included 28 studies in qualitative synthesis and 14 in the meta-analyses.In seven studies, no association was seen between SGLT2 inhibitor use and COVID-19-related mortality (OR 0.91; 95% CI: 0.57–1.46). In three studies, no association was seen with COVID-19-related hospitalization (OR 0.90; 95% CI: 0.67–1.20). A reduced risk of pneumonia was observed in three studies (HR: 0.61; 95% CI: 0.57–0.66).A reduced risk of pneumonia-related mortality was found in two studies (HR: 0.49; 95% CI: 0.35–0.67)A reduced risk of sepsis was observed in three studies (HR: 0.45; 95% CI: 0.30–0.68).The authors conclude that real-world evidence suggests SGLT2 inhibitors are associated with a lower risk of pneumonia, pneumonia-related mortality and sepsis, but not COVID-19-related hospitalizations or mortality in adults with type 2 diabetes. Given the high burden of infection in patients with type 2 diabetes, the authors recommend further studies to validate the benefit of SGLT2 inhibitors in reducing pneumonia, pneumonia-related mortality and sepsis in patients with type 2 diabetes and to clarify their mechanism of action in reducing infection risk. If the associations identified in their analysis are confirmed in subsequent clinical studies, the authors indicate that clinicians might tailor prescribing of glucose-lowering medications to reduce the risk of severe infections (e.g., sepsis). In addition, patient education initiatives could highlight the potential benefits of SGLT2 inhibitors in reducing infection risks, potentially enhancing adherence and optimizing health outcomes in patients with type 2 diabetes.Reference1. Arvez MJA, Tan GSQ, Leung MTY, et al. SGLT2 inhibitors and the risk of infections in type 2 diabetes: systematic review and meta-analyses of real-world evidence. J Diabetes Res 2025;Oct 16:2025:5888495. https://onlinelibrary.wiley.com/doi/10.1155/jdr/5888495 (accessed November 4, 2025).

SGLT2 inhibitors and infection risk in patients with type 2 diabetes

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