SGLT2 Inhibitors and the Risk of Infections in Type 2 Diabetes: Systematic Review and Meta-Analyses of Real-World Evidence.

Background: People with diabetes are at increased risk of infections. Emerging evidence suggests sodium-glucose cotransporter 2 (SGLT2) inhibitors have pleiotropic effects that may protect against certain infections. We systematically reviewed real-world evidence on the association between SGLT2 inhibitors and infections among adults with Type 2 diabetes. Methods: We searched Medline, Embase, Scopus, and Google Scholar from January 1, 2012 to March 18, 2024 for observational studies conducted in adults with Type 2 diabetes published in English. The exposure was SGLT2 inhibitors, and comparators were nonusers or users of other glucose-lowering medications. Studies reporting outcome estimates for specific non-genitourinary infections were included. The study was prospectively registered with PROSPERO (CRD42023492265). Results: From 6827 records, 28 studies were included in qualitative synthesis and 14 in meta-analyses. There was no association with COVID-19-related mortality in seven studies (OR 0.91; 95% CI: 0.57-1.46) or COVID-19-related hospitalisation in three studies (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 in two studies (HR: 0.49; 95% CI: 0.35-0.67), and a reduced risk of sepsis in three studies (HR: 0.45; 95% CI: 0.30-0.68). Conclusion: Real-world evidence suggests SGLT2 inhibitors are associated with lower risk of pneumonia, pneumonia-related mortality and sepsis. Given the high burden of infection in this population, these associations deserve further research.