SGLT‐2 Inhibitor Use and Cause‐Specific Hospitalization Rates: An Outcome‐Wide Study to Identify Novel Associations of SGLT‐2 Inhibitors

Abstract

Sodium‐glucose co‐transporter 2 inhibitors (SGLT2is) have demonstrated multifaceted pharmacological effects. In addition to type 2 diabetes, they are now indicated for heart failure and chronic kidney disease. This study aimed to identify novel associations between SGLT2i use and health outcomes using real‐world data. Using linked data from a nationwide diabetes registry in Australia, we compared hospitalization rates in people living with type 2 diabetes commencing treatment with SGLT2i and dipeptidyl peptidase‐4 inhibitor (DPP4i) between December 1, 2013, and June 30, 2019. Cause‐specific hospitalizations were categorized across three hierarchies of diagnoses (first, first three, and first four digits of International Classification of Diseases, Tenth Version, Australian Modification codes). Incidence rate ratio (IRR) and 95% confidence interval (95% CI) for each cause‐specific hospitalization were estimated using negative binomial regression. In the first hierarchy, hospitalization rates were lower across most diagnosis groups among SGLT2i initiators (n = 99,569) compared with DPP4i initiators (n = 186,353). In the second and third hierarchies, there were lower hospitalization rates relating to infections, anemias, and obstructive airway diseases among SGLT2i initiators compared with DPP4i initiators. These included sepsis (IRR: 0.60, 95% CI: 0.51–0.72) anemia (IRR: 0.55, 95% CI: 0.46–0.66), and chronic obstructive pulmonary diseases (IRR: 0.52, 95% CI: 0.40–0.68), as well as for previously known associations (e.g., heart failure (IRR: 0.63, 95% CI: 0.56–0.70)). SGLT2is have previously uncharacterized associations on a range of important clinical outcomes; validation of these associations requires further study, some of which may suggest novel benefits or new indications for SGLT2is.