Association Between SGLT2 Inhibitor Treatment and Diabetic Ketoacidosis and Mortality in People With Type 2 Diabetes Admitted to Hospital With COVID-19
Kamlesh Khunti, Yue Ruan, Jim Davies, Benjamin C. T. Field, Sophie Harris, Mikhail Kosiborod, Dinesh Nagi, Parth Narendran, Dipesh Patel, Robert E. J. Ryder, Kinga A. Várnai, Sarah H. Wild, Emma G. Wilmot, Rustam Rea, for the ABCD COVID-19 Diabetes National Audit Investigators, Rustam Rea, Emma G. Wilmot, Kamlesh Khunti, Sarah H. Wild, Ben Field, Parth Narendran, Rajiv Gandhi, Sophie Harris, Dinesh Nagi, Robert E. J. Ryder, Jim Davies, S. E. Harris, Oliver Freeman, Benjamin D. Maylor, Kinga A. Várnai, Gail Roadknight, Melissa Cull, Yue Ruan, Amy Edwards, Susan Gelding, Kirun Gunganah, Pyei Aung, Moulinath Banerjee, Ali Chakera, Dominique Rouse, Syed Haris Ahmed, Ho Yee Cheung, Hywel Roberts, Susan Seal, Syed Saah Shah, Amir Hayat, Cynthia Mohandas, Htet Htet Aung, Su Khant Chel, Nyan Lin, Kavitia Narula, Furruq Quadri, Su Lei Yin, Yin Yin, Alamin Alkundi, Abdelmajid Musa, Emma Birbeck, Charles Bodmer, Irene Bossman, Sathis Kumar, Umesh Dashora, Elizabeth Toubi, Mansoor Zafar, Vinod Patel, Amitha Gopinath, Belinda Allan, Remat Karim, Dharshana Appuhamillage, Khubaib Ayoub, Charmaine Ilangaratne, Maliha Iqbal, Rory Maclean, Omar Mustafa, Susan Baxter, Malgorzata Adamus, Kevin Baynes, Siva Sivappriyan, Ryan D’Costa, Vernon Parfitt, Mazharul Islam, Sadia Nasir, Kinga A. Várnai, Senthil K. Vasan, Vilashini Arul Devah, Foteini Kavvoura, Lina Ficken, James Gilham, Vincent Simpson, Neil Walker, Umaira Aziz, Efthimia Karra, Dipesh Patel, Miranda Rosenthal, Tracy Curran, Angela Paisley, Parijat de P, Priscilla Sarkar, James H. Clark, Vesna Hogan, Lauren S. Jackson
Abstract
OBJECTIVE: To determine the association between prescription of SGLT2 inhibitors (SGLT2is) and diabetic ketoacidosis (DKA) incidence or mortality in people with type 2 diabetes (T2D) hospitalized with COVID-19. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study based on secondary analysis of data from a large nationwide audit from a network of 40 centers in the U.K. with data collection up to December 2020. The study was originally designed to describe risk factors associated with adverse outcomes among people with diabetes who were admitted to hospital with COVID-19. The primary outcome for this analysis was DKA on or during hospital admission. The secondary outcome was mortality. Crude, age-sex adjusted, and multivariable logistic regression models were used to generate odds ratios (ORs) and 95% CIs for people prescribed SGLT2i compared with those not prescribed SGLT2i. RESULTS: The original national audit included 3,067 people with T2D who were admitted to hospital with COVID-19, of whom 230 (7.5%) were prescribed SGLT2is prior to hospital admission. The mean age of the overall cohort was 72 years, 62.3% were men, and 34.9% were prescribed insulin. Overall, 2.8% of the total population had DKA and 35.6% of people in the study died. The adjusted odds of DKA were not significantly different between those prescribed SGLT2is and those not (OR 0.56; 95% CI 0.16-1.97). The adjusted odds of mortality associated with SGLT2is were similar in the total study population (OR 1.13; 95% CI 0.78-1.63), in the subgroup prescribed insulin (OR 1.02; 95% CI 0.59-1.77), and in the subgroup that developed DKA (OR 0.21; 95% CI 0.01-8.76). CONCLUSIONS: We demonstrate a low risk of DKA and high mortality rate in people with T2D admitted to hospital with COVID-19 and limited power, but no evidence, of increased risk of DKA or in-hospital mortality associated with prescription of SGLT2is.