Association of Sodium-Glucose Cotransporter-2 Inhibitors vs Dipeptidyl Peptidase-4 Inhibitors With Pneumonia, COVID-19, and Other Adverse Respiratory Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Objective: Our aim in this study was to systematically assess the association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM). Methods: PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2i (exposure group) or DPP4i (control group). Stata version 15.0 statistical software was used for the meta-analysis. Results: Ten studies were included, all 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2i had a lower incidence of pneumonia (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.51 to 0.74) and pneumonia risk (OR 0.63, 95% CI 0.60 to 0.68, p=0.000) compared with those receiving DPP4i. The same situation was seen for mortality for pneumonia (OR 0.49, 95% CI 0.39 to 0.60) and pneumonia mortality risk (OR 0.47, 95% CI 0.42 to 0.51). There was lower mortality due to COVID-19 (OR 0.31, 95% CI 0.28 to 0.34) and a lower hospitalization rate (OR 0.61, 95% CI 0.56 to 0.68, p=0.000) and incidence of mechanical ventilation (OR 0.69, 95% CI 0.58 to 0.83, p=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2i. Qualitative analysis results show that SGLT2i were associated with a lower incidence of COVID-19, lower risk of obstructive airway disease events, and lower hospitalization rate of health-care-associated pneumonia than DPP4i. Conclusion: In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i. (c) 2024 Canadian Diabetes Association.