Several previous studies, including randomised clinical trials and observational studies, have shown heart and kidney benefits associated with sodium-glucose cotransporter-2 inhibitors (SGLT2i), an oral antidiabetic drug, among patients with type 2 diabetes. In addition to such benefits, findings from preclinical studies have suggested the potential for additional benefits in other organ systems, for instance, the lung and the liver. However, there is limited clinical and real-world evidence on the potential lung and liver benefits of SGLT2is. The current study will use the United Kingdom Clinical Practice Research Datalink to investigate whether the use of SGLT2is, compared with another glucose-lowering drug class, dipeptidyl peptidase-4 inhibitors (DPP4i), is associated with a lower risk of experiencing lung-related and liver-related outcomes. This will provide much needed information regarding this possible association to patients and prescribers.
Various evidence has shown that sodium-glucose cotransporter-2 inhibitors (SGLT2is), an oral antidiabetic drug, reduce the incidence of cardiorenal events. However, whether this drug class also reduces the risk of respiratory or hepatic events to have a multi-organ benefit in patients with type 2 diabetes in the real-world setting is uncertain. To address this uncertainty, we will compare the incidence of respiratory or hepatic events among new users of SGLT2is versus new users of dipeptidyl peptidase-4 inhibitors (DPP4is) among patients with type 2 diabetes. As part of a binational population-based cohort study of the UK and South Korea, this study will utilize United Kingdom Clinical Practice Research Datalink (CPRD) between January 1, 2010 and December 31, 2020 to identify new-user, active comparator cohorts of SGLT2i and DPP4i with patients at least 18 years of age. Cox proportional hazards regression models will be used to calculate hazard ratios with 95% confidence intervals of SGLT2is associated with respiratory or hepatic events compared with DPP4is. Subgroup analyses will evaluate whether there is effect modification by age (≥65, <65 years), sex, history of comorbidities in the past year (eg, liver cirrhosis or chronic obstructive pulmonary disease), insulin use in the past year, and SGLT2i molecule.
Respiratory outcomes of acute pulmonary oedema, acute respiratory distress syndrome, pneumonia, and respiratory failure, and hepatic outcomes of severe hepatic injury and hepatic decompensation events of hospitalization for hepatic failure, liver transplantation, liver necrosis (central haemorrhagic necrosis of liver), ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, bleeding oesophageal varices, or hepatic encephalopathy, and hepatic-related deaths.
Ju-Young Shin - Chief Investigator - Sungkyunkwan University
Ju-Young Shin - Corresponding Applicant - Sungkyunkwan University
Han Eol Jeong - Collaborator - Sungkyunkwan University
Sohee Park - Collaborator - Sungkyunkwan University
Sungho Bea - Collaborator - Sungkyunkwan University
Yunha Noh - Collaborator - Sungkyunkwan University
HES Admitted Patient Care;ONS Death Registration Data