Comparative estimate of glucose-lowering therapies on risk of incident pneumonia and severe sepsis: an analysis of real-world cohort data

Thorax. 2024 Dec 23;80(1):32-41. doi: 10.1136/thorax-2024-221906.

Abstract

Background: 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.

Aims: This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis.

Methods: 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.

Results: After propensity score matching, 352 687 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, 331 863 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)).

Conclusion: 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.

Keywords: Bacterial Infection; Clinical Epidemiology; Infection Control; Pneumonia; Respiratory Infection.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Female
  • Glucagon-Like Peptide-1 Receptor* / agonists
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Incidence
  • Male
  • Middle Aged
  • Pneumonia* / epidemiology
  • Retrospective Studies
  • Sepsis* / drug therapy
  • Sepsis* / epidemiology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Dipeptidyl-Peptidase IV Inhibitors