{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T17:33:26Z","timestamp":1794418406725,"version":"4.9.1"},"reference-count":36,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2024,10,3]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and sepsis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Aims<\/jats:title>\n<jats:p>This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective cohort study was conducted using anonymised electronic medical records from TriNetX, a global federated database. Two intention-to-treat analyses were performed, each with two cohorts of adult T2D patients. The first analysis compared individuals prescribed SGLT2i, and the second individuals prescribed GLP-1 RAs, with those prescribed dipeptidyl peptidase-4 inhibitors (DPP-4i). An active comparator new user design was used, with outcomes defined as time-to-incident pneumonia and severe sepsis. Propensity score matching (1:1) was applied to control for potential confounders, and patients were followed for 12 months. Secondary analyses compared SGLT2i and GLP-1 RAs against other glucose-lowering therapies.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>After propensity score matching, 352\u2009687 patients were included in the SGLT2i versus DPP-4i comparison. SGLT2i treatment was associated with a risk reduction in incident pneumonia (HR 0.75 (95% CI 0.73, 0.78)) and severe sepsis (0.75 (0.73, 0.77)). In the GLP-1 RA versus DPP-4i comparison, 331\u2009863 patients were included. GLP-1 RA treatment was associated with a risk reduction in incident pneumonia (0.60 (0.58, 0.62)) and severe sepsis (0.61 (0.59, 0.63)).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>SGLT2i and GLP-1 RAs are associated with a reduced risk of incident pneumonia and severe sepsis in patients with T2D. Further research and focused randomised controlled trials are warranted to explore the broader clinical implications of these treatments.<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/thorax-2024-221906","type":"journal-article","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T18:20:11Z","timestamp":1733595611000},"page":"32-41","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Comparative estimate of glucose-lowering therapies on risk of incident pneumonia and severe sepsis: an analysis of real-world cohort data"],"prefix":"10.1136","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex E","family":"Henney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-6524","authenticated-orcid":false,"given":"David R","family":"Riley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa J","family":"Hydes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Anson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema H","family":"Ibarburu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Frost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Cuthbertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"2025012402151331000_80.1.32.1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310522"},{"key":"2025012402151331000_80.1.32.2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0880"},{"key":"2025012402151331000_80.1.32.3","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0138"},{"key":"2025012402151331000_80.1.32.4","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13288"},{"key":"2025012402151331000_80.1.32.5","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.152777"},{"key":"2025012402151331000_80.1.32.6","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23073651","article-title":"An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors","volume":"23","author":"Salvatore","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2025012402151331000_80.1.32.7","doi-asserted-by":"crossref","DOI":"10.1186\/s12933-021-01366-8","article-title":"GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs","volume":"20","author":"Giugliano","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"2025012402151331000_80.1.32.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(16)30006-4"},{"key":"2025012402151331000_80.1.32.9","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-019-00686-z"},{"key":"2025012402151331000_80.1.32.10","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac558"},{"key":"2025012402151331000_80.1.32.11","doi-asserted-by":"crossref","unstructured":"Wang M , et al . 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