Association of adverse respiratory events with sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in South Korea: a nationwide cohort study

Abstract

Background Impaired respiratory function remains underrecognized in patients with type 2 diabetes (T2D), despite common pulmonary impairment. Meanwhile, there is little data available on the respiratory effects of sodium glucose cotransporter 2 inhibitors (SGLT2i). Hence, we examined the association between SGLT2i use and the risk of adverse respiratory events in a real-world setting. Methods We conducted a population-based, nationwide cohort study using an active-comparator new-user design and nationwide claims data of South Korea from January 2015 to December 2020. Among individuals aged 18 years or older, propensity score matching was done to match each new user of SGLT2is with dipeptidyl peptidase 4 inhibitors (DPP4is), with patients followed up according to an as-treated definition. The primary outcome was respiratory events, a composite endpoint of acute pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure. Secondary outcomes were the individual components of the primary outcome and in-hospital death. Cox models were used to estimate hazard ratios (HRs) and 95% CIs. Results Of 205,534 patient pairs in the propensity score matched cohort, the mean age of the entire cohort was 53.8 years and 59% were men, with a median follow-up of 0.66 years; all baseline covariates achieved balance between the two groups. Incidence rates for overall respiratory events were 4.54 and 7.54 per 1000 person-years among SGLT2i and DPP4i users, respectively, corresponding to a rate difference of 3 less events per 1000 person-years (95% CI − 3.44 to − 2.55). HRs (95% CIs) were 0.60 (0.55 to 0.64) for the composite respiratory endpoint, 0.35 (0.23 to 0.55) for acute pulmonary edema, 0.44 (0.18 to 1.05) for ARDS, 0.61 (0.56 to 0.66) for pneumonia, 0.49 (0.31 to 0.76) for respiratory failure, and 0.46 (0.41 to 0.51) for in-hospital death. Similar trends were found across individual SGLT2is, subgroup analyses of age, sex, history of comorbidities, and a range of sensitivity analyses. Conclusions These findings suggest a lower risk of adverse respiratory events associated with patients with T2D initiating SGLT2is versus DPP4is. This real-world evidence helps inform patients, clinicians, and guideline writers regarding the respiratory effects of SGLT2i in routine practice.

Effect of dapagliflozin on COVID-19 infection and risk of hospitalization

“…In addition, there are some data from a South Korean cohort study that shows the benefits of SGLT2i on respiratory events regarding Dipeptidyl peptidase 4 inhibitors, which are another class of oral antidiabetic drugs. 24 SGLT2i might reduce the effects of SARS-CoV-2 on chronic respiratory diseases. One mechanism of SARS-CoV-2 entry into host cells is mainly through angiotensin-converting enzyme 2 (ACE2).…”

A comprehensive meta-analysis on safety outcomes reveals the novel potentials of SGLT2is, especially preventing respiratory diseases

“…Second, SGLT2is were significantly associated with the decreased risks of several kinds of respiratory disorders (e.g., acute respiratory failure, asthma, and COPD), and infectious disorders (e.g., bronchitis and pneumonia). Similarly, a cohort study ( 34 ) showed that SGLT2is had a significant association with the lower risks of adverse respiratory events including respiratory failure, pulmonary edema, and pneumonia. These findings may suggest that SGLT2is could be used for the prevention of relevant respiratory and infectious diseases.…”

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Harms or Unexpected Benefits?

“…In a large, national cohort trial, the use of SGLT2 inhibitors was linked with decreased risks of total respiratory events, pneumonia, and respiratory failure among T2DM patients compared to the use of DPP-4 inhibitors [47]. All SGLT2 inhibitor compounds exhibited these respiratory improvements, indicating a possible class effect [47].…”

“…In a large, national cohort trial, the use of SGLT2 inhibitors was linked with decreased risks of total respiratory events, pneumonia, and respiratory failure among T2DM patients compared to the use of DPP-4 inhibitors [47]. All SGLT2 inhibitor compounds exhibited these respiratory improvements, indicating a possible class effect [47]. In another retrospective cohort analysis of individuals with T2DM in Hong Kong, SGLT2 inhibitor use was linked with a decreased incidence of incident obstructive airway disease (OAD) and a lower rate of OAD exacerbations in clinical settings compared to DPP-4 inhibitors use.…”