Association Between SGLT2 Inhibitor Treatment and Diabetic Ketoacidosis and Mortality in People With Type 2 Diabetes Admitted to Hospital With COVID-19
Authors: Khunti Kamlesh , Ruan Yue , Davies Jim , Field Benjamin C.T. , Harris Sophie , Kosiborod Mikhail , Nagi Dinesh , Narendran Parth , Patel Dipesh , Ryder Robert E.J. , Várnai Kinga A. , Wild Sarah H. , Wilmot Emma G. , Rea Rustam ,   for the ABCD COVID-19 Diabetes National Audit Investigators, Rea Rustam , Wilmot Emma , Khunti Kamlesh , Wild Sarah , Field Ben , Narendran Parth , Gandhi Rajiv , Harris Sophie , Nagi Dinesh , Ryder Robert , Davies Jim , Harris Steve , Freeman Oliver , Maylor Ben , Várnai Kinga A. , Roadknight Gail , Cull Melissa , Ruan Yue , Edwards Amy , Gelding Susan , Gunganah Kirun , Aung Pyei , Banerjee Moulinath , Chakera Ali , Rouse Dominique , Ahmed Syed Haris , Cheung Ho Yee , Roberts Hywel , Seal Susan , Shah Syed Saah , Hayat Amir , Mohandas Cynthia , Aung Htet Htet , Chel Su Khant , Lin Nyan , Narula Kavitia , Quadri Furruq , Yin Su Lei , Yin Yin , Alkundi Alamin , Musa Abdelmajid , Birbeck Emma , Bodmer Charles , Bossman Irene , Kumar Sathis , Dashora Umesh , Toubi Elizabeth , Zafar Mansoor , Patel Vinod , Gopinath Amitha , Allan Belinda , Karim Remat , Appuhamillage Dharshana , Ayoub Khubaib , Ilangaratne Charmaine , Iqbal Maliha , Maclean Rory , Mustafa Omar , Baxter Susan , Adamus Malgorzata , Baynes Kevin , Sivappriyan Siva , D’Costa Ryan , Parfitt Vernon , Islam Mazharul , Nasir Sadia , Várnai Kinga , Vasan Senthil , Devah Vilashini Arul , Kavvoura Foteini , Ficken Lina , Gilham James , Simpson Vincent , Walker Neil , Aziz Umaira , Karra Efthimia , Patel Dipesh , Rosenthal Miranda , Curran Tracy , Paisley Angela , De P Parijat , Sarkar Priscilla , Clark James , Hogan Vesna , Jackson Lauren , Williamson Jamie-Leigh , Younes R. , Robin Lucy , Grixti Lydia , Tee Suann , Sathya Abilash , Patel Mayank , Holmes Catherine , Hanif Wasim , Ghosh Sandip , Ahmad Ehtasham , Ahmed Ejaz , Davies Melanie , Hartshorn Steven , Simons Lee , Webb David , Brahm Anupam , Pramodh Seshadri , Frew Katy , Mackenzie Alison , Wild Abigail , Casey Helen , Morrison Deborah , McKeag Conor , Sillars Anne , Stirling Angus , Smeeton Fiona , Muhammad Syed , Obuobie Kofi , Yin Win , Agarwal Neera , Atkinson Mike , Ambati Sai , Khan Rahim , Nalla Preethi , Tabasum Arshiya , Zouras Stamatios , Mallipedhi Akhila , Chudleigh Richard , Williams David 
Published: September 2022

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.