Does euDKA Exist even in Patients not Using SGLT-2 Inhibitors?
- The short answer is YES. Munro JF et al [5] reviewed a case series of 37 episodes of euDKA in a publication from 1973. Although, dated and not robust evidence some take home messages can be derived:
- All but one episode was in insulin dependent diabetics
- Vomiting was the most frequent symptom of euDKA in 32% of patients
- Management in most cases consisted of: Intravenous fluids and electrolyte replacement.
- No deaths occurred in this case series
What are the Names of the SGLT-2 Inhibitors?
- Ipragliflozin (Suglat) – Approved in Japan
- Dapagliflozin (Farxiga) – 1st SGLT2 Inhibitor Approved; Approved in US
- Luseogliflozin (Lusefi) – Approved in Japan
- Tofogliflozin (Apleway; Deberza) – Approved in Japan
- Canagliflozin (Invokana) – Approved in US & Canada
- Empagliflozin (Jardiance) – Approved in US
How do SGLT-2 Inhibitors Cause euDKA?
What is the Evidence that SGLT-2 Inhibitors Cause euDKA?
- Again, not robust but there are a few publications of case reports and case series
- Peters AL et al. 2015: Case Series of 13 Cases [1]
- Hine et al. Case Report of 2 Cases [3]
- Hayami et al. Single Case Report [4]
Discussion:
- euDKA could be completely missed if just looking at the serum blood glucose alone. This could lead to worse outcomes for patients not started on treatment
- The exact incidence of euDKA in patients taking SGLT-2 inhibitors is really unknown, as this entity may be under reported or even completely missed
- The treatment of euDKA will be nearly identical to DKA:
- IVF: Treat dehydration; In addition to balanced crystalloids, may need to start fluids with dextrose sooner in the treatment process, due to the serum blood glucose already being low (i.e. <200mg/dL),
- IV Insulin: Close the anion gap and reverse the metabolic acidosis
Clinical Take Home Point: In patients with diabetes mellitus, on a SGLT-2 inhibitor and/or carbohydrate food restriction, who present with nausea/vomiting, fatigue, or the development of a metabolic acidosis, checking a urine and/or serum ketones is critical to not miss a case of euDKA.
References:
- Peters AL et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment with Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015; 38 (9): 1687 – 93. PMID: 26078479
- Ogawa W and Sakaguchi K. Euglycemic Diabetic Ketoacidosis Induced by SGLT2 Inhibitors: Possible Mechanism and Contributing Factors. J Diabetes Investig 2016; 7 (2): 135 – 8. PMID: 27042263
- Hine J et al. SGLT Inhibition and Euglycemic Diabetic Ketoacidosis. Lancet Diabetes Endocrinal 2015; 3: 503 – 504. PMID: 26025388
- Hayami T et al. Case of Ketoacidosis by a Sodium-Glucose Cotransporter 2 Inhibitor in a Diabetic Patient with a Low-Carbohydrate Diet. J Diabetes Investig 2015; 6: 587 – 590. PMCID: PMC4578500
- Munro JF et al. Euglycemic Diabetic Ketoacidosis. BMJ 1973; 2 (5866: 578 – 80. PMID: 4197425
For More Thoughts on This Topic Checkout:
- Craig Cocchio at Emergency Medicine PharmD: Euglycemic DKA from SGLT2 Inhibitors: Don’t Worry, I Can’t Pronounce Them Either
- Anton Helman at EM Cases: Best Case Ever 58 Euglycemic DKA
- Priyanka Kailash at EM Docs: Euglycemic DKA Secondary to SGLT2 Inhibitors
Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)
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