Sodium-Glucose Cotransporter-2 Inhibitors Decrease Risk for Pneumonia, Sepsis

Researchers compared the risk for pneumonia and sepsis in patients with type 2 diabetes on sodium-glucose contransporter-2 vs dipeptidyl peptidase-4 inhibitors.

Patients with type 2 diabetes (T2D) taking sodium-glucose cotransporter-2 (SGLT2) inhibitors were at decreased risk for pneumonia and sepsis compared with those taking dipeptidyl peptidase-4 (DPP-4) inhibitors, according to study findings published in Diabetes & Metabolism.

Researchers used the Clinical Data Analysis and Reporting System, a clinical registry in Hong Kong, to capture demographic and health information from patients with T2D who initiated treatment with either SGLT2 inhibitors (n=10,706) or DPP-4 inhibitors (n=18,281) between 2015 and 2019.

Researchers utilized 1:2 propensity-score matching to balance baseline characteristics between patients in the SGLT2 group and those in the DPP-4 group. Data were analyzed using Cox proportional hazards regression.

The primary outcomes were incident pneumonia and sepsis; secondary outcomes were the number of deaths related to pneumonia, sepsis, and infectious diseases; urinary tract infections; urogenital infections; and diabetic ketoacidosis

Among all patients included in the analysis, the mean age was 60±11.07 years, 61.1% were men, and approximately 45% had T2D for more than 10 years. Patients in the SGLT2 and DPP-4 groups most commonly received empagliflozin (64.04%) and linagliptin (26.43%), respectively.

The researchers found that pneumonia occurred among 309 patients in the SGLT2 group within a median follow-up period of 2.29 years (incidence rate [IR], 11.38), compared with 961 of those in the DPP-4 group within a median follow-up period of 2.33 years (IR, 20.45).

During a median follow-up period of 2.31 and 2.35 years, sepsis occurred among 164 patients in the SGLT2 inhibitor group (IR, 6.00) and 610 in the DPP-4 inhibitor group (IR, 12.88), respectively.

Irrespective of T2D duration, patients initiated on SGLT2 inhibitors had a 37% decreased risk for incident pneumonia (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.55-0.72; P <.001) and a 48% decreased risk for incident sepsis (aHR, 0.52; 95% CI, 0.44-0.62; P <.001) compared with those initiated on DPP-4 inhibitors.

Compared with DPP-4 inhibitors, the researchers found that SGLT2 inhibitors were associated with a decreased risk of death related to pneumonia (aHR, 0.41; 95% CI, 0.29-0.58; P <.001), sepsis (aHR, 0.39; 95% CI, 0.18-0.84; P <.05), and infectious disease (aHR, 0.43; 95% CI, 0.32-0.57; P <.001).

This study was limited by potential residual confounding due to its observational design.

“These results hold important clinical implications in reducing the attendant complications of diabetes,” the researchers noted. “Mechanistic insights into lower infection complications with SGLT2 inhibitors merit further investigations,” they concluded.


Wu MZ, Chandramouli C, Wong PF, et al. Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors. Diabetes Metab J. Published online June 23, 2022. doi:10.1016/j.diabet.2022.101367