Objectives: Sodium-glucose transporter-2 inhibitors (SGLT2i) are commonly used for the treatment of Type 2 Diabetes Mellitus, offering additional benefits in non-diabetic patients with conditions such as chronic kidney disease and heart failure. However, SGLT2i have been associated with an increased risk of euglycemic diabetic ketoacidosis (DKA). This case series describes three cases of patients who developed euglycemic DKA while taking SGLT2i. Key Findings: Each of the three patients with euglycemic DKA were taking SGLT2i for the treatment of diabetes and all had additional risk factors for the development of DKA. These factors included reduced oral intake, major acute illness, chronic pancreatitis, and a history of previous DKA episodes. Unfortunately, the absence of hallmark symptoms like hyperglycemia, polyuria, and polydipsia led to delayed diagnosis of euglycemic DKA in two of the three patients. Conclusion: Early recognition of risk factors and a high level of suspicion are critical in identifying euglycemic DKA in patients taking SGLT2i. Healthcare providers should conduct thorough medication reconciliation upon admission and closely monitor patients for concurrent issues, especially in cases of minimal oral intake, acute illnesses, and chronic pancreatitis. Prompt diagnosis and management of euglycemic DKA can significantly improve patient outcomes.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are highly selective, effective, and generally well-tolerated antihyperglycemic agents targeting the SGLT-2 transmembrane protein. Despite being primarily registered for diabetes treatment, due to their cardiorenal protective properties, SGLT-2 inhibitors caused a paradigm shift in the treatment of other diseases on the cardiorenal spectrum, becoming a fundamental part of heart failure and chronic kidney disease management. With their rapidly increasing use, there are also increased reports of a rare, often under-recognised and potentially deadly side effect, SGLT-2-inhibitor-induced euglycemic diabetic ketoacidosis (EDKA). The primary pathophysiological process behind its multifactorial aetiology comprises glucosuria and osmotic diuresis, which produce a significant carbohydrate deficit, leading to an increase in the glucagon-insulin ratio, thus resulting in accelerated ketogenesis. Although EDKA has a similar clinical presentation as diabetic ketoacidosis (DKA), the absence of the high glucose levels typically expected for DKA and the presence of urine ketone reabsorption contribute to a significant delay in its recognition and timely diagnosis. Given the broad use of SGLT-2 inhibitors, increased awareness, early recognition, and prompt identification of precipitating factors are essential. In this narrative review, we comprehensively explore the pathophysiological mechanisms of SGLT-2-inhibitor-induced EDKA, analyse its clinical manifestation, and identify the most common triggers for its development. We also discuss EDKA management and preventive strategies.

Acute pancreatitis is a common and potentially life-threatening condition. It is characterized by inflammation of the pancreas, most often leading to elevated levels of pancreatic enzymes in the blood. In a subset of patients, however, conventional biomarker levels may remain within the reference range. Such instances have the potential to create a diagnostic challenge for healthcare professionals and can lead to misdiagnosis or delayed treatment. This article presents the intriguing clinical scenario of acute pancreatitis with normal amylase and lipase, discusses factors that may lead to normoenzymatic presentation, and reminds clinicians of the diagnostic criteria for acute pancreatitis, which does not necessarily require elevated pancreatic enzymes.

Diabetic ketoacidosis (DKA) is a severe complication of diabetes mellitus characterized by hyperglycemia, metabolic acidosis, and ketosis. We present a challenging case of euglycemic DKA secondary to fasting and urinary tract infection with acute renal failure in a 50-year-old woman. Despite normal random blood sugar levels, the patient exhibited clinical signs of DKA, leading to further investigation. High anion gap metabolic acidosis with hyperkalemia and abnormal renal function tests were identified. After hemodialysis, serum ketones were found to be highly positive, confirming the diagnosis. Prompt management led to a complete clinical and laboratory resolution. This case underscores the importance of considering DKA in patients with suggestive symptoms, even with normal blood sugar levels.

This article reviews the most current literature on diabetic ketoacidosis, including how to make the diagnosis and management. It discusses euglycemic diabetic ketoacidosis and the risk factors for this rare but dangerous disease process. Pertinent pearls and pitfalls encountered by the emergency physician when managing these patients are included. Because these patients often stay in the emergency department for prolonged periods, recommendations on transitioning to subcutaneous insulin are included, along with dosing recommendations. Finally, the article reviews how to disposition patients with diabetic ketoacidosis and examines important factors that lead to a successful discharge home.

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.

OBJECTIVE: The effectiveness of standard treatment for diabetic ketoacidosis (DKA) in \"euglycemic DKA\" (EuDKA, blood glucose (BG) ≤ 250 mg/dL) was evaluated with respect to the time to correction of BG ≤ 200 mg/dL, anion gap (AG)≤12 mmol/L, and serum bicarbonate [HCO3] ≥18 mmol/L.
METHODS: Data were retrieved from an electronic health record (EPIC) for \"diabetic ketoacidosis.\" Patients were categorized by initial BG as EuDKA, middle range DKA (MrDKA, >250 < 600 mg/dL) and hyperosmolar DKA (HyperDKA ≥600 mg/dL).
RESULTS: There were 56 patients (27men, 29women; age 45.8 ± 15.6 (SD) years. The initial 8-h insulin infusion rate (0.05 ± 0.02, 0.09 ± 0.03, 0.14 ± 0.05units/kg/h, p < 0.001) and the time to correction of BG (3.4 ± 1.9, 6.1 ± 2.9 and 9.6 ± 3.9 h, p < 0.001), differed for EuDKA, MrDKA and HyperDKA. There were no differences in the time to correction of AG or [HCO3]. The earlier time to correction of BG in EuDKA resulted in paradoxical longer lag times for correction of [HCO3] (p = 0.003) and AG (p = 0.048). Changes in BG, AG and [HCO3] correlated with insulin infusion rates of 0.08-0.1units/kg/h whereas in EuDKA the insulin infusion rate was 0.05 ± 0.02 units/kg/h.
CONCLUSIONS: In EuDKA, correlation analyses suggest that higher glucose and insulin infusion rates than what would be projected for the level of blood glucose are required to reverse ketoacidosis. Prospective trials are required to optimize the levels of glucose and insulin infusions in EuDKA.

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.

Metformin-associated lactic acidosis is a well-known metformin treatment complication; however, the development of euglycemic diabetic ketoacidosis (euDKA) has rarely been reported. Here we report a case of lactic acidosis and euDKA after metformin overdose. A 57-year-old female patient was transferred to our hospital with severe metabolic acidosis and acute kidney injury. She had type 2 diabetes mellitus and was on oral antidiabetic therapy of vildagliptin metformin hydrochloride daily. On the admission day, she had committed suicide by overdosing 50 tablets of vildagliptin metformin hydrochloride, which was equivalent to 25,000 mg of metformin and 2500 mg of vildagliptin. She had severe lactic acidosis 5 h after overdosing. However, after 34 h of overdosing, serum lactate levels decreased while serum anion gap levels increased. She received single hemodialysis treatment. Serum total ketone bodies, β-hydroxybutyrate acetoacetic acid, and acetone were increased even after hemodialysis treatment. Her blood glucose levels have never exceeded 250 mg/dL since admission. Therefore, we considered that the cause of metabolic acidosis in this patient was not only lactic acidosis but also euDKA. The causes of euDKA in our patient might be hepatic production of ketone bodies due to metformin overdose in addition to type 2 diabetes mellitus, starvation, infection, and stressful physical conditions such as vomiting and diarrhea. We propose that not only lactic acidosis but also ketoacidosis is one of the important pathological conditions in patients with metformin overdose.

Sodium-glucose cotransporter-2 inhibitors are now considered second-line treatment agents for type 2 diabetes and offer a unique treatment approach with added cardiorenal benefits. Drugs in this class increase the risk of euglycemic diabetic ketoacidosis, which may be difficult to diagnose if clinicians are not aware of the risk factors and subtle symptoms. This article describes a case of euglycemic diabetic ketoacidosis in a patient with coronary artery disease who was taking a sodium-glucose cotransporter-2 inhibitor and experienced acute mental status changes immediately after heart catheterization.