Association Between DPP-4 Inhibitors and COVID-19–Related Outcomes Among Patients With Type 2 Diabetes
Yunha Noh, In‐Sun Oh, Han Eol Jeong, Kristian B. Filion, Oriana Hoi Yun Yu, Ju‐Young Shin
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), uses angiotensin-converting enzyme 2 to invade human cells. However, recent evidence suggested that dipeptidyl peptidase 4 (DPP-4) may be used as a coreceptor when SARS-CoV-2 enters the target cells (1). Interestingly, upregulation of DPP-4 is associated with older age, respiratory or cardiovascular disease, and diabetes (2), all of which were reported to exacerbate COVID-19. Given the pathophysiological evidence, DPP-4 inhibitors were suggested to have beneficial effects on COVID-19. Given the high fatality rate of COVID-19 among patients with diabetes, there is an urgent need to understand the effect DPP-4 inhibitors may have on COVID-19. Therefore, we aimed to determine whether use of DPP-4 inhibitors reduces the risk of adverse COVID-19–related outcomes among patients with type 2 diabetes (T2D). We conducted a nationwide cohort study using the Health Insurance Review and Assessment Service database linked with the Korea Disease Control and Prevention Agency database, which covers the entire South Korean population of ≥50 million, from 1 January 2017 to 15 May 2020. We included patients who had a positive test result for COVID-19 as of 15 May 2020, had been diagnosed with T2D within the preceding 3 years before COVID-19 diagnosis (cohort entry), and had ≥1 antidiabetic prescription within the 180 days before cohort entry. We excluded patients aged <18 years; those prescribed metformin monotherapy only, to restrict inclusion to patients who were on second- or third-line therapy for T2D; those prescribed insulin monotherapy as they are likely to be patients with type 1 diabetes; those prescribed only insulin and metformin as they do not belong to …