Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis

Abstract

Introduction Patients with diabetes mellitus type 2 and chronic kidney disease (T2DM-CKD) have a 5 times higher risk of developing severe SARS-CoV-2 infection than those without these 2 diseases. The goal of this study is to provide information on T2DM-CKD and COVID-19 outcomes, with an emphasis on the association with anti-diabetic medications. Methodology Study is designed as a retrospective cohort analysis covering the years 2020 and 2021. Data from the National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, Causes of Death Registry data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed. Results Of 231 796 patients with diabetes mellitus type 2 in the database, 7 539 were T2DM-CKD (3.25%). The 2-year cumulative incidences of all three studies’ outcomes were higher in T2DM-CKD than in diabetes patients without CKD (positivity 18.1% vs. 14.4%; hospitalization 9.7% vs. 4.2%; death 3.3% vs. 1.1%, all p<0.001). For COVID-19 hospitalization, protective factors were SGLT-2 inhibitors use (OR 0.430; 95%CI 0.257–0.719) and metformin use (OR 0.769; 95% CI 0.643–0.920), risk factors were insulin use (1.411; 95%CI 1.167–1.706) and sulfonylureas use (OR 1.226; 95% CI 1.027–1.464). For SARS-CoV-2 positivity protective factors were SGLT-2 inhibitors (0.607; 95% CI 0.448–0.823), repaglinide use (OR 0.765; 95% CI 0.593–0.986) and metformin use (OR 0.857; 95% CI 0.770–0.994). DPP-4 inhibitors showed a non-significant decrease in risk for COVID-19 death (OR 0.761; 95% CI 0.568–1.019). Conclusion T2DM-CKD are heavily burdened by COVID-19 disease. Our results suggest no association between antidiabetic drugs and COVID-19 death outcome while SGLT-2 and metformin show to be protective against COVID-19 hospitalization and infection, repaglinide against infection, and insulin and sulfonylureas show to be risk factors for COVID-19 hospitalization and infection. Further research in T2DM-CKD is needed.