(54) Sodium Glucose Cotransporter 2 Inhibitors and The Risk of Respiratory Outcomes Among Patients with Type 2 Diabetes: A Nationwide Cohort Study

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 728

Presenting Author(s)

Han Eol Jeong, MPH, PhD
– Postdoctoral Research Fellow, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggido, South Korea

Co-Author(s)

Sohee Park
– School of Pharmacy, SKKU, Jangan-Gu, Suwon-Si, Gyeonggido, South Korea
Yunha Noh
– Sungkunkwan University, Suwon, Gyeonggido, South Korea
Kristian Filion, PhD
– Associate Professor, McGill University, Montreal, QC, Canada
Oriana Hoi Yun Yu, MD, MSc
– Assistant Professor, McGill University, Montreal, QC, Canada
Seung Hun Jang
– Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Republic of Korea
Ju-Young Shin, PhD
– Associate Professor, School of Pharmacy, Sungkyunkwan University, Suwon, Kyonggi-do, Republic of Korea

Background: Pre-clinical studies have suggested the potential of respiratory benefits associated with sodium glucose cotransporter 2 inhibitors (SGLT2i), in addition to the established cardiorenal benefits, among patients with type 2 diabetes (T2D).

Objectives: To assess the risk of respiratory outcomes associated with SGLT2i versus dipeptidyl peptidase-4 inhibitor (DPP4i) among patients with T2D.

Methods: Using Korea’s nationwide insurance claims data (2015-2020), we conducted an active comparator, new user cohort study by identifying new users of SGLT2i and DPP4i who entered the study cohort on first date of prescription, with no record of prescription for both drugs within the prior year. We defined exposure using an as-treated approach, with patients followed from cohort entry until the earliest of event occurrence, treatment interruption (discontinuation or switch to a comparator drug), in-hospital death, or end of the study. The primary outcome was a composite respiratory end point, comprised of acute pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure; secondary outcomes were the individual components of the primary outcome. To adjust potential imbalances in baseline covariates, we propensity score-matched SGLT2i users to DPP4i users in a 1:1 ratio. We estimated hazard ratios (HRs) with 95% CIs for the risk of respiratory outcomes among SGLT2i users versus DPP4i users using Cox regression models.

Results: We identified 205 534 pairs of SGLT2i and DPP4i users, with a mean age of 53.8 year and 41% male. During follow-up, 1025 SGLT2i users (incidence rate 4.54 per 1000 person-years) and 1810 DPP4i users (7.54) had a respiratory outcome. The HRs in the as-treated analyses, comparing SGLT2i versus DPP4i, were 0.64 (95% CI 0.59-0.69) for the composite respiratory outcome, 0.40 (0.26-0.63) for acute pulmonary edema, 0.46 (0.19-1.12) for ARDS, 0.65 (0.60-0.70) for pneumonia, and 0.53 (0.34-0.84) for respiratory failure. The HRs were consistent for the individual SGLT2i molecule and also among subgroups of patients with history of asthma, chronic obstructive pulmonary disease, and baseline insulin use. The magnitude of the association with the composite respiratory outcome (0.71, 0.65-0.76) became smaller in the intention-to-treat analysis.

Conclusions: In this large Korean cohort, SGLT2i use compared with DPP4i use was significantly associated with reduced risks of the composite respiratory outcome, acute pulmonary edema, pneumonia, and respiratory failure. This real-world evidence helps inform patients and practitioners regarding the respiratory effectiveness of SGLT2i in routine clinical practice.