Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 26, 2023; 11(24): 5700-5709
Published online Aug 26, 2023. doi: 10.12998/wjcc.v11.i24.5700
Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports
Anwar Khedr, Hussam Al Hennawi, Muhammed Khuzzaim Khan, Aalaa Eissa, Mikael Mir, Ibtisam Rauf, Jain Nitesh, Salim Surani, Syed Anjum Khan
Anwar Khedr, Department of Medicine, Bronx Care Health System, Bronx, NY 10457, United States
Hussam Al Hennawi, Department of Internal Medicine, Jefferson Abington Hospital, Abington, PA 19001, United States
Muhammed Khuzzaim Khan, Department of Internal Medicine, Dow University of Health Science, Karachi 74200, Pakistan
Aalaa Eissa, Department of Medicine, Kafrelsheikh University, KFS 33511, Egypt
Mikael Mir, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, United States
Ibtisam Rauf, Department of Medicine, St. George’s University, School of Medicine, St. George SW17 0RE, Grenada
Jain Nitesh, Department of Critical Care, Mayo Clinic Health System, Mankato, MN 56001, United States
Salim Surani, Department of Medicine & Pharmacology, Texas A&M University, College Station, TX 77843, United States
Syed Anjum Khan, Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
Author contributions: Khedr A, Hennawi HA, Khan MK, Eissa A, Mir M, and Rauf I contributed to the conception and design of the manuscript; Khan MK, Eissa A, Mir M, Rauf I and Nitesh J contributed to the collection of the data; Khedr A, Hennawi HA, Mir M, Rauf I, and Nitesh J contributed to the interpretation of the analysis; Khedr A, Hennawi HA, Khan MK, Eissa A, and Nitesh J drafted the manuscript; Surani S and Khan SA provided the oversight; All the authors critically revised the manuscript, gave final approval, and agreed to be accountable for all aspects of the work, ensuring integrity and accuracy.
Conflict-of-interest statement: None of the authors have any conflict to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Salim Surani, FCCP, MD, MHSc, Academic Editor, Professor, Department of Medicine & Pharmacology, Texas A&M University, 400 Bizzell St, College Station, TX 77843, United States. srsurani@hotmail.com
Received: May 29, 2023
Peer-review started: May 29, 2023
First decision: June 19, 2023
Revised: July 13, 2023
Accepted: July 28, 2023
Article in press: July 28, 2023
Published online: August 26, 2023
Processing time: 87 Days and 17.5 Hours
ARTICLE HIGHLIGHTS
Research background

The coexistence of coronavirus disease 2019 (COVID-19) infection and the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have generated debate due to the potential risk of euglycemic diabetic ketoacidosis (eu-DKA) development. Limited information regarding this specific patient population is available, necessitating a systematic review to investigate the outcomes and characteristics associated with eu-DKA in COVID-19-infected diabetic patients treated with SGLT2 inhibitors.

Research motivation

Given the controversy and limited data surrounding the association between SGLT2 inhibitors, COVID-19 infection, and eu-DKA, there is a pressing need to investigate this topic to enhance our understanding of the potential risks and outcomes.

Research objectives

The primary objectives of this study are to examine the association between SGLT2 inhibitors and the development of eu-DKA in COVID-19-infected diabetic patients, explore the potential mechanisms underlying this relationship, and assess the clinical outcomes and management strategies for this patient population.

Research methods

We conducted a comprehensive search of relevant databases to identify studies reporting on the association between SGLT2 inhibitors and eu-DKA in COVID-19-infected diabetic patients. We followed the PRISMA guidelines for study selection and data extraction. The extracted data were qualitatively synthesized to provide a narrative overview of the findings.

Research results

The systematic review included eight studies comprising 12 patients, investigating the association between SGLT2 inhibitors and eu-DKA in COVID-19-infected diabetic patients. The majority of patients presented with eu-DKA symptoms 2-3 d after the onset of COVID-19 symptoms. The survival rate was over 90%, with one reported fatality. Significant pH deviations were observed, with the lowest reported pH being 6.87. All patients discontinued SGLT2 inhibitors and received treatment with fluids and IV insulin. The results highlight the potential risk of developing eu-DKA in this patient population.

Research conclusions

This systematic review concludes that the use of SGLT2 inhibitors in COVID-19-infected diabetic patients may increase the risk of eu-DKA. The pancreatic toxicity induced by the severe acute respiratory syndrome coronavirus 2 virus is believed to contribute to this phenomenon. The analysis of case reports provides evidence supporting the association between SGLT2 inhibitors and eu-DKA in this patient population. Further studies with larger sample sizes and robust designs are necessary to enhance our understanding and inform clinical decision-making for high-risk individuals.

Research perspectives

Further research is needed to investigate the mechanisms of eu-DKA in COVID-19 patients on SGLT2 inhibitors. Larger randomized studies are necessary to establish a causal relationship and identify risk factors. Standardized protocols for diagnosis and management should be developed to improve patient outcomes. These research perspectives will enhance understanding and guide evidence-based approaches in the future.