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Review
. 2025 Oct 16:2025:5888495.
doi: 10.1155/jdr/5888495. eCollection 2025.

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

Maria J Alfonso Arvez  1 , George S Q Tan  1 , Miriam T Y Leung  1 , Zanfina Ademi  1 , J Simon Bell  1
Affiliations
Review

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

Maria J Alfonso Arvez et al. J Diabetes Res. .

Abstract

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.

Keywords: COVID-19; SGLT2 inhibitor; Type 2 diabetes; infection; observational study; pneumonia; sepsis.

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Conflict of interest statement

J.S.B. was supported by a National Health and Medical Research Council (NHMRC) Boosting Dementia Research Leadership Fellowship and has received grant funding or consulting funds from the NHMRC, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organisations unrelated to this work. All grants and consulting funds were paid to the employing institution.

Figures

Figure 1
Figure 1
Study selection diagram.
Figure 2
Figure 2
Risk of bias across studies using risk of bias in nonrandomised studies of interventions (ROBINS-I) tool.
Figure 3
Figure 3
Forest plots that demonstrate the association between sodium–glucose cotransporter-2 inhibitors (SGLT2i) use with (a) COVID-19 mortality, (b) COVID-19 hospitalisation, (c) pneumonia, (d) pneumonia-mortality, and (e) sepsis in patients with Type 2 diabetes compared with other glucose-lowering medication (OGLM) or to dipeptidyl peptidase-4 inhibitors (DPP4i).
See this image and copyright information in PMC

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