Life-Saving Awareness: Recognizing and Preventing Euglycemic Ketoacidosis in Patients on SGLT-2 and GLP-1 Therapy

Diabetic Ketoacidosis (DKA) is a well-known, life-threatening emergency complication most commonly associated with type 1 diabetes, though it may also occur in type 2 diabetes. This dangerous condition is characterized by marked hyperglycemia, metabolic acidosis, and elevated plasma ketones. Treatment involves intravenous fluids, insulin therapy, and careful electrolyte replacement.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (familiar brand names include Jardiance, Farxiga, Ozempic, Wegovy, Mounjaro, Zepbound, Victoza) are increasingly popular options, not only for glycemic control among patients with diabetes, but also for heart failure management and weight loss—even in non-diabetics. Many of these drugs also demonstrate cardiovascular and renal benefits. However, as the use of these medications has increased, so has the incidence of a specific variant of DKA.

Euglycemic Ketoacidosis (EKA), associated with SGLT-2 and GLP-1 use, can occur in both diabetics and non-diabetics. Like DKA, it is characterized by metabolic acidosis and ketonemia. However, instead of the extremely elevated blood glucose levels typical of DKA, patients with EKA present with normal or only slightly elevated glucose. The absence of this hallmark feature can delay diagnosis and treatment, as well as hinder patient recognition of the crisis. Clinicians, caregivers, and patients should be aware of the risk factors, prevention strategies, symptoms, and appropriate actions to take.

Risk Factors for Developing EKA

• SGLT-2 or GLP-1 usage (SGLT-2s are more strongly associated than GLP-1s)

• Higher medication doses

• Any action or condition that increases ketone production, including:

  • Fasting (e.g., intermittent fasting, preoperative/preprocedural fasting)

  • Ketogenic diet

  • Gastrointestinal illness (poor appetite, nausea, vomiting, diarrhea)

  • Eating disorders (anorexia/bulimia)

  • Alcohol intoxication

  • Liver cirrhosis

  • Pancreatitis

  • Gastroparesis

  • Insulin pump malfunction

• Low muscle mass

• Recent infection or surgery

• Type 2 diabetes with longstanding poor glucose control

Prevention Strategies

• Emphasize the importance of hydration with water and electrolyte solutions

• Minimize alcohol intake

• Ensure meals and snacks contain 30–35% carbohydrate content

• Avoid ketogenic or prolonged fasting diets

• Clinicians should consider temporarily discontinuing SGLT-2 and GLP-1 therapy before surgery or during acute illness

• Patients should not decrease basal insulin dose by more than 20% without consulting their provider

• Patients should avoid taking these medications within 3 days prior to fasting longer than overnight

Symptoms of EKA

• Fruity-smelling breath

• Excessive thirst

• Polyuria or nocturia

• Nausea and vomiting

• Abdominal pain

• Confusion or altered mental status

• Fever

• Shortness of breath

Patient Education and Action

Patients taking SGLT-2 or GLP-1 medications should be instructed that if they experience nausea, vomiting, or diarrhea:

• Sip calorically dense electrolyte solutions (approximately 200 mL every 30 minutes), or

• Suck on hard candy, or

• Consume one tablespoon of sugar every 15–20 minutes

If symptoms persist, patients should withhold further doses of the medication and contact their primary care provider or seek emergency care. Patients should disclose their use of SGLT-2 and GLP-1 medications to all healthcare providers and express concerns about ketoacidosis.

Euglycemic ketoacidosis (EKA) is a relatively rare but serious complication linked to the use of SGLT-2 inhibitors and, less frequently, GLP-1 receptor agonists. Unlike classic diabetic ketoacidosis, EKA is characterized by normal or only mildly elevated blood glucose levels, making recognition more challenging. Awareness of risk factors, early symptoms, and prevention strategies is essential for patients, caregivers, and clinicians alike. With adequate education and careful clinical management, the EKA risk associated with these therapies can be minimized, supporting safe and effective use in both diabetic and non-diabetic populations.

References

American Diabetes Association Professional Practice Committee. (2024a). Obesity and weight management for the prevention and treatment of type 2 diabetes: Standards of care in diabetes—2024. Diabetes Care, 47(Suppl. 1), S145–S157. https://doi.org/10.2337/dc24-S008

American Diabetes Association Professional Practice Committee. (2024b). Pharmacologic approaches to glycemic treatment: Standards of care in diabetes—2024. Diabetes Care, 47(Suppl. 1), S158–S178. https://doi.org/10.2337/dc24-S009

American Diabetes Association Professional Practice Committee. (2024c). Cardiovascular disease and risk management: Standards of care in diabetes—2024. Diabetes Care, 47(Suppl. 1), S179–S218. https://doi.org/10.2337/dc24-S010

American Diabetes Association Professional Practice Committee. (2024d). Diabetes care in the hospital: Standards of care in diabetes—2024. Diabetes Care, 47(Suppl. 1), S295–S306. https://doi.org/10.2337/dc24-S016

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Mehta, A. E., & Zimmerman, R. (2025). Classic diabetic ketoacidosis and the euglycemic variant: Something old, something new. Cleveland Clinic Journal of Medicine, 92(1), 33–39. https://doi.org/10.3949/ccjm.92a.24075

Patel, N., Reddy, A., Romero, K. N., & Reddy, P. (2025). Euglycemic diabetic ketoacidosis in the setting of dulaglutide use. Cureus, 17(4), e82143. https://doi.org/10.7759/cureus.82143

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