Meta-Analysis
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2023; 14(8): 1314-1322
Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1314
Sodium-glucose Cotransporter-2 Inhibitors induced euglycemic diabetic ketoacidosis: A meta summary of case reports
Deven Juneja, Prashant Nasa, Ravi Jain, Omender Singh
Deven Juneja, Omender Singh, Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
Prashant Nasa, Department of Critical Care Medicine, NMC Specialty Hospital, Dubai 7832, United Arab Emirates
Prashant Nasa, Department of Internal Medicine, College of Medicine and Health Sciences, Al Ain 15551, Abu Dhabi, United Arab Emirates
Ravi Jain, Department of Critical Care Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur 302022, Rajasthan, India
Author contributions: Juneja D acquisition of data, analysis and interpretation of data, drafting the article, final approval; Nasa P acquisition of data, analysis and interpretation of data, drafting the article, final approval; Jain R interpretation of data, revising the article, final approval; Singh O designing the study, drafting the article, final approval.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Deven Juneja, FCCP, MD, Director, Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, 1, Press Enclave Road, New Delhi 110017, India. devenjuneja@gmail.com
Received: April 27, 2023
Peer-review started: April 27, 2023
First decision: May 19, 2023
Revised: May 20, 2023
Accepted: June 19, 2023
Article in press: June 19, 2023
Published online: August 15, 2023
Processing time: 105 Days and 17.1 Hours
Abstract
BACKGROUND

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are commonly prescribed to manage patients with diabetes mellitus. These agents may rarely lead to the development of euglycemic diabetic ketoacidosis (EDKA), which may complicate the disease course of these patients.

AIM

To analyze the demographic profile, predisposing factors, symptomology, clinical interventions and outcomes of patients presenting with EDKA secondary to SGLT2i use by reviewing the published case reports and series.

METHODS

We performed a systematic search of PubMed, Science Direct, Google Scholar and Reference Citation Analysis databases using the terms “canagliflozin” OR “empagliflozin” OR “dapagliflozin” OR “SGLT2 inhibitors” OR “Sodium-glucose cotransporter-2” AND “euglycemia” OR “euglycemic diabetic ketoacidosis” OR “metabolic acidosis”. The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported EDKA secondary to SGLT2i. Furthermore, the data were filtered from the literature published in the English language and on adults (> 18 years). We excluded: (1) Conference abstracts; and (2) Case reports or series which did not have individual biochemical data. All the case reports and case series were evaluated. The data extracted included patient demographics, clinical symptomatology, clinical interventions, intensive care unit course, need for organ support and outcomes.

RESULTS

Overall, 108 case reports and 17 cases series with 169 unique patients that met all the inclusion criteria were included. The majority of patients were females (54.4%, n = 92), and the commonly reported symptoms were gastrointestinal (nausea/vomiting 65.1%, abdominal pain 37.3%) and respiratory (breathlessness 30.8%). One hundred and forty-nine (88.2%) patients had underlying type II diabetes, and the most commonly involved SGLT-2 inhibitor reported was empagliflozin (46.8%). A triggering factor was reported in most patients (78.7%), the commonest being acute severe infection (37.9%), which included patients with sepsis, coronavirus disease 2019, other viral illnesses, and acute pancreatitis. 61.5% were reported to require intensive unit care, but only a minority of patients required organ support in the form of invasive mechanical ventilation (13%), vasopressors (6.5%) or renal replacement therapy (5.9%). The overall mortality rate was only 2.4%.

CONCLUSION

Patients on SGLT2i may rarely develop EDKA, especially in the presence of certain predisposing factors, including severe acute infections and following major surgery. The signs and symptoms of EDKA may be similar to that of DKA but with normal blood sugar levels, which may make the diagnosis challenging. Outcomes of EDKA are good if recognized early and corrective actions are taken. Hence, physicians managing such patients must be aware of this potential complication and must educate their patients accordingly to ensure early diagnosis and management.

Keywords: Canagliflozin; Empagliflozin; Euglycemia; Diabetes mellitus; Diabetic ketoacidosis; Sodium-glucose cotransporter-2 inhibitors; Sodium-glucose cotransporter-2

Core Tip: Sodium-glucose cotransporter-2 inhibitors are a newer class of oral hypoglycemic drugs commonly prescribed for managing patients with diabetes mellitus. Even though these drugs are effective in controlling blood glucose and have favorable cardiac effects, they may rarely lead to the development of euglycemic diabetic ketoacidosis (EDKA), which may complicate the disease course of these patients. Certain risk factors, such as severe acute illness and major surgery, may predispose these patients to develop EDKA. The signs and symptoms of EDKA are similar to classic symptoms of diabetic ketoacidosis, but these patients have normal blood glucose levels, making the diagnosis difficult. Hence, a higher index of suspicion is warranted in such patients, as delay in diagnosis may lead to higher morbidity and mortality.