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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been implemented in treating diabetic patients for the past 10 years. Euglycemic diabetic ketoacidosis (euDKA) can be a life-threatening complication in diabetic patients. The authors report a severe euDKA with lactic acidosis in a type 2 diabetes mellitus (T2DM) patient. This report highlights the importance of the early detection and treatment of EuDKA to avoid complications.
UNASSIGNED: Forty-four-year-old female with T2DM had multiple visits to the emergency department with recurrent diarrhoea and vomiting. On her third visit, she presented with shortness of breath and tachypnoea, found to have severe metabolic acidosis with euglycemia. She was admitted to ICU with euDKA secondary to SGLT2i and was managed accordingly.
UNASSIGNED: The association between SGLT2i and euDKA in T2DM is controversial. SGLT2i leads to euDKA by stimulating lipolysis and ketogenesis in the setting of volume depletion, carbohydrate deficiency, and upregulation of counter-regulatory stress hormones. EuDKA can be life-threatening, especially if not diagnosed and managed properly. The treatment protocol is similar to hyperglycaemic diabetic ketoacidosis. Our case has been reported in line with the CARE criteria.34.
UNASSIGNED: SGLT2i benefits in diabetic patients outweigh the risks. Clinicians are advised to counsel diabetic patients maintained on SGLT2 and educate them regarding holding the medication in the setting of acute illness, volume depletion, decreased oral intake, and surgery. In addition, there should be a high index of suspicion for patients presenting with metabolic acidosis in the background of SGLT2i use to provide early diagnosis and management.

Diabetic ketoacidosis (DKA) is considered a medical emergency, most commonly associated with type 1 diabetes mellitus, and is relatively rare in type 2 diabetes mellitus (T2DM). We discuss a case of a 45-year-old woman with T2DM who presented to the emergency room with worsening lethargy and weakness. Before her presentation, her physician had recently added empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, to her anti-diabetic drug regimen along with glimepiride and a combination drug of vildagliptin and metformin. Based on the clinical examination and lab findings, DKA was suspected, but her glucose level was below the cutoff value for DKA diagnosis. However, her lab results showed significant metabolic acidosis and ketonemia with no clinical or laboratory features of sepsis. Therefore, the diagnosis of euglycemic diabetic ketoacidosis (eu-DKA) was made. She was successfully treated according to the DKA protocol and discharged in good condition. In this report, our aim is to discuss the relationship between SGLT-2 inhibitors with eu-DKA. Given the absence of significant hyperglycemia, recognition of this entity by clinicians may be delayed. Serum ketones should be obtained in diabetic patients with symptoms of nausea, vomiting, or malaise while taking SGLT-2 inhibitors, and SGLT-2 inhibitors should be discontinued if ketoacidosis is confirmed.

There is growing evidence to support the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for type 2 diabetes mellitus (T2DM) and the management of heart failure. As such, more patients undergoing cardiac surgery are on SGLT2-inhibitor therapy. Despite the numerous benefits of SGLT2 inhibitors on cardiac health, they can be associated with an increased risk of diabetic ketoacidosis, often with normal glucose levels (euglycemic diabetic ketoacidosis or EDKA), which potentially can be detrimental in this vulnerable patient population. In this narrative review, the authors discuss 17 papers that described EDKA in perioperative cardiac surgical patients. The authors discuss suggested preventative measures and management options, with a particular emphasis on raising the clinical awareness of the care teams toward this complication. SGLT2 inhibitor-induced EDKA is a medical emergency that can be difficult to identify in the postcardiac surgical patient due to the overlap of signs and symptoms with other frequent scenarios in these patients. A reduction in SGLT2 inhibitor-associated EDKA can be mitigated by the appropriate perioperative discontinuation of the medication, clinical awareness, and early investigation to diagnose the condition, with emphasis on serum β-hydroxybutyrate. Future quality improvement initiatives are needed to assist in reducing EDKA in patients taking SGLT2 inhibitors in the perioperative surgical setting.

UNASSIGNED: Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) rarely cause euglycemic diabetic ketoacidosis (euDKA) in diabetic patients. The aim was to identify demographic, clinical, and predisposing factors for euDKA from published case reports.
UNASSIGNED: A systematic review of published case reports of euDKA in patients receiving SGLT2 inhibitors and meta-analysis of clinical trials to quantify the risk ratio (RR) of DKA in patients receiving SGLT2 inhibitors. PubMed and EMBASE databases were searched for the case reports of and clinical trials from January 2010 to August 2020. Studies published in English language were included and other languages were excluded. Data related to patients\' demography, clinical presentation, drug and dose of SGLT2 inhibitors, and concomitant medication were extracted. Incidence of diabetic ketoacidosis (DKA) extracted from clinical trials. Data related to demographic, clinical, and other parameters presented as ratios and proportions and incidence of DKA in RR using Review Manager 5.3.
UNASSIGNED: Forty-seven of 160 reports with an aggregate of 77 patients were included in the analysis. The majority of the patients were females (67.53%), with T2DM and with gastrointestinal symptoms (58%). Surgery was the most common precipitating factor (n/N = 15/77). Canagliflozin (n/N = 34/77) was the commonest SGLT2 inhibitor reported along with metformin as the concomitant medication (63.6%). The pooled RR of DKA was 3.70 (95%CI 2.58, 5.29) and I2 = 0%.
UNASSIGNED: euDKA is commonly seen in middle-aged female, T2DM patients taking SGLT2 inhibitors along with metformin. The risk of DKA in patients receiving SGLT2 inhibitors increases by 3.7 times than the other medication.

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes and is considered a medical emergency. Euglycemic DKA (EKDA) is a variant of DKA with a normal or minimally elevated glucose level <200 mg/dl. The condition can be difficult to diagnose due to the relatively normal glucose levels. Pregnancy, infection, and a low-calorie intake are some of the contributing common etiologies of EDKA. Despite a rapid increase in scientific publications on COVID-19, there are still knowledge gaps regarding the course of COVID-19 in some patient subset. This is especially the case for pregnant women. In this case report, we discuss the course of COVID-19 infection in a pregnant woman with gestational diabetes who developed severe euglycemic diabetic ketoacidosis triggered by various precipitating factors, including starvation, caused by COVID-19 infection and its gastrointestinal effects.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce cardiovascular, kidney, and overall mortality. SGLT2i are also associated with a rare adverse event, euglycemic diabetic ketoacidosis (EDKA). This report describes a case of EDKA one day after bariatric surgery in a 51-year-old female with type 2 diabetes mellitus managed with the SGLT2i, canagliflozin. She was following a ketogenic diet for three weeks prior to surgery. The patient made a steady recovery with rapid anion gap closure followed by prolonged non-anion gap metabolic acidosis. Her medical record was tagged with a life-threatening reaction to SGLT2i. The risk of EDKA from SGLT2i may be increased by a low carbohydrate diet or postoperative status. Our case was complicated by hypokalemia, exemplifying the need for aggressive electrolyte management. Further guidance is needed to manage risk factors provoking EDKA and the use of SGLT2i therapy after an episode of EDKA.

Diabetic ketoacidosis (DKA) is an acute and significant life-threatening complication of diabetes. The association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) with euglycemic diabetic ketoacidosis (EDKA) has been well reported. This literature review was conducted to understand the mechanism of EDKA and identify the potential risk factors and precipitants for patients taking SGLT2i. After reviewing the published literature between 2010 and 2020, 32 articles are included in the final review. The underlying mechanism is mainly enhanced lipolysis and ketone body reabsorption. SGLT2i also stimulates pancreatic alpha cells and inhibits beta cells, causing an imbalance in glucagon/insulin levels, further contributing to lipolysis and ketogenesis. Most patients were diagnosed with blood glucose less than 200 mg/dL, blood pH <7.3, increased anion gap, increased blood, or urine ketones. Perioperative fasting, pancreatic etiology, low carbohydrate or ketogenic diet, obesity, and malignancy are identified precipitants in this review. As normoglycemia can conceal the underlying acidosis, physicians should be cognizant of the EDKA diagnosis and initiate prompt treatment. Patient education on risk factors and triggers is recommended to avoid future events.

OBJECTIVE: SGLT2-inhibitors (SGLT-2i) have been linked to the risk of potential life-threatening diabetic ketoacidosis (DKA). The U.S. Food and Drug Administration and the European Medicines Agency issued warnings in 2015 and 2016 respectively on the predisposing factors to the development of DKA in individuals on an SGLT2i. New predisposing factors to DKA are still being discovered with the use of SGLT-2i. The list by FDA and EMA is yet to be updated. This article aims to provide a holistic list that includes the newer factors that have been implicated in the development of DKA. The overall aim is to guide physicians in prescribing this class of drugs for type 2 diabetes mellitus (T2D).
METHODS: A search was done using PUBMED, Google Scholar, and Directory of Open Access Journals with the following words: SGLT-2 Inhibitors AND Ketoacidosis were entered. We included articles from 2000 to 2020, those in English, those involving any of the approved SGLT2i medications in T2D patients, and studies that focused on DKA linked to SGLT-2i. These articles were reviewed, and relevant data extracted and compiled.
CONCLUSIONS: The review has revealed that predisposing factors include (excess) alcohol consumption, female gender, starvation due to illness or fasting, withholding the use of SGLT2i for less than 48 h peri-operatively, and the existence of a variations in the expression of SGLT2 receptors. Patients should be advised on \"sick day rules,\" and if a patient becomes unwell while on an SGLT2i, they should be advised to withhold the medication for the duration of the intercurrent illness.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are antihyperglycemic drugs that are currently being recommended as second-line therapy for patients with diabetes mellitus. SGLT-2 Inhibitors function by inhibiting renal cotransporters, which reduces the reabsorption of glucose in the kidney, ultimately decreasing the concentration of glucose in the body. They have gained popularity in recent years due to their protective effects on the heart and kidneys - both organ systems that diabetes mellitus has shown to have a deleterious effect on. However, despite their growing fame, they have been found to increase the risk of euglycemic diabetic ketoacidosis (DKA). Euglycemic DKA is particularly dangerous as there is a chance that it can be missed by clinicians due to glucose levels generally being less than 200 mg/dL. There is an increasing body of literature detailing cases of euglycemic DKA after bariatric surgery. We present a brief review of the literature regarding this important side effect of SGLT-2 inhibitors seen in patients after bariatric surgery.