In the largest study of its kind to date, treatment with glucagon-like peptide-1 receptor agonists was associated with a 40% reduction in pneumonia risk among patients with type 2 diabetes compared to dipeptidyl peptidase-4 inhibitors.
The study assessed the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on pneumonia and severe sepsis risks in adults with type 2 diabetes. Using anonymized data from the TriNetX global federated database, the researchers conducted a retrospective cohort analysis with propensity score matching to control for confounders. Published in Thorax, the study included 352,687 matched pairs for SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP-4i) and 331,863 matched pairs for GLP-1 RA versus DPP-4i, with a 12-month follow-up period.
The primary outcomes were time-to-incident pneumonia and severe sepsis. SGLT2i use was associated with a 25% reduced risk of pneumonia (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.73-0.78) and severe sepsis (HR 0.75; 95% CI 0.73-0.77) compared to DPP-4i. GLP-1 RAs were associated with a 40% reduced risk of pneumonia (HR 0.60; 95% CI 0.58-0.62) and a 39% reduced risk of severe sepsis (HR 0.61; 95% CI 0.59-0.63). Incidence rates per 1000 person-years in the SGLT2i group were 25.6 for pneumonia and 20.6 for severe sepsis, compared to 34.6 and 28.0 in the DPP-4i group. Corresponding rates for GLP-1 RA were 17.8 and 15.1, compared to 29.3 and 24.6 in the DPP-4i group.
The researchers calculated that treating 111 patients with SGLT2i or 91 patients with GLP-1 RA would prevent 1 case of pneumonia compared to DPP-4i treatment. Secondary analyses showed similar risk reductions when comparing these medications against other glucose-lowering therapies.
The pleiotropic effects of these therapies may explain the findings, including weight loss-mediated reduction in chronic inflammation and cardiorenal protection. For SGLT2i specifically, the researchers noted potential benefits from improved oxygen delivery to lung tissue through optimization of hematocrit and hemoglobin levels. GLP-1 RAs may work through higher expression of GLP-1 receptors in the lung compared to other organs, potentially reducing airway inflammation.
Study limitations include potential residual confounding, inability to track drug switching during follow-up, reliance on electronic health record coding practices, and challenges in identifying sepsis sources. The researchers emphasized the need for focused randomized controlled trials to explore the mechanisms behind these associations.
Full disclosures can be found in the published study.
