Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports

BACKGROUND Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below 200 mg/dL. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can induce eu-DKA in diabetic patients. Notably, coronavirus disease 2019 (COVID-19) -infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets. This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis. Additionally, we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors, providing indispensable insights for healthcare professionals managing this specific patient population. AIM To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports. METHODS We conducted an exhaustive search across prominent electronic databases, including PubMed, SCOPUS, Web of Science, and Google Scholar. This search encompassed the period from December 2019 to May 2022, incorporating published studies and pre-prints. The search terms employed encompassed "SGLT2 inhibitors", "euglycemic DKA", "COVID-19", and related variations. By incorporating these diverse sources, our objective was to ensure a thorough exploration of the existing literature on this subject, thereby augmenting the validity and robustness of our findings. RESULTS Our search yielded a total of seven case reports and one case series, collectively comprising a cohort of twelve patients. These reports detailed instances of eu-DKA in individuals with COVID-19. Crucially, all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication. Upon admission, all oral medications were promptly discontinued, and the patients were initiated on intravenous insulin therapy to effectively manage the DKA. Encouragingly, eleven patients demonstrated a favorable outcome, while regrettably, one patient succumbed to the condition. Subsequently, SGLT2 were discontinued for all patients upon their discharge from the hospital. These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2, underscoring the critical importance of prompt intervention and vigilant medication adjustments. CONCLUSION Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA, as well as encountering adverse outcomes in the context of COVID-19, despite maintaining satisfactory glycemic control. The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous. Consequently, this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.