II. Epidemiology: SGLT2 Inhibitor Associated Ketosis
- Initially 73 reported cases in 2 years for patients on SGLT2 Inhibitors with Serum Glucose <250 mg/dl
- Subsequently 2500 cases with patients on SGLT2 Inhibitors reported to FDA
III. Mechanism: SGLT2 Inhibitor Associated Ketosis
- Sodium-Glucose Co-Transporter-2 Inhibitor (SGLT2 Inhibitor) are Oral Hypoglycemic agents in Type II Diabetes
- SGLT2 Inhibitors block Glucose reabsorption in the Kidneys, with Glucose excreted in the urine
- Results in lower Blood Sugars, results in decreased Insulin release
- May result in increased Fatty Acid breakdown and Ketone production due to Hypoglycemia
- SGLT2 Inhibitor may also directly increase Fatty Acid breakdown and Ketone production
IV. Risk Factors: SGLT2 Inhibitor Associated Ketosis
- Increased risk with renal Impairment (as well as Dehydration, acute illness)
- Avoid Farxiga (Dapagliflozin) if GFR <60 ml/min
- Avoid Invokana (Canagliflozin) and Jardiance (Empagliflozin) if GFR <45 ml/min
V. Symptoms
- Onset as early as first 2 weeks of starting an SGLT2 Inhibitors
- Nausea and Vomiting
- Fatigue
- Malaise
VI. Signs
- Dehydration
- Tachypnea
- Sinus Tachycardia
- Confusion
VII. Labs
- Metabolic Acidosis with Anion Gap
-
Serum Ketones increased (but Urine Ketones often normal)
- Serum Beta-Hydroxybutyrate >3.8 mmol/l
- Serum Glucose paradoxically normal
VIII. Differential Diagnosis
- See Metabolic Acidosis with Anion Gap
- Diabetic Ketoacidosis
- Alcohol Ketoacidosis (chronic Alcohol Abuse)
- Starvation Ketoacidosis
- Pregnancy
- Sepsis
- Pancreatitis
- Post-operative Bariatric Surgery
IX. Management: SGLT2 Inhibitor Associated Ketosis
- Similar management as with Diabetic Ketoacidosis Management
- Potassium Replacement if <3.5 meq/dl before Insulin initiated
- Initiate fluid bolus
- Start D5 or D10 infusion
- Start Insulin 0.1 units/kg/h infusion (do not give Insulin bolus)
X. Prevention
- Hold SGLT2 Inhibitor before sustained exertional activity (e.g. marathon run)
- Discontinue SGLT2 Inhibitors when significant acute medical stressors are present (e.g. hospital admission)
XI. Resources
- SGLT2 Inhibitors and Euglycemic DKA (FDA)
XII. References
- Swaminathan and Hayes in Herbert (2019) EM:Rap 19(6): 12
- Long and Lentz (2021) EM:Rap 21(8): 15-6
