Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Acute onset of euglycaemic DKA with initiation of SGLT2 inhibitor therapy for type 2 diabetes (#341)

Shan Jiang 1 , Olivia Watson 1 , Marwan Obaid 1
  1. Diabetes Centre, Bankstown-Lidcombe Hospital, Bankstown, NSW, Australia

Introduction:

With favourable cardiovascular outcomes associated with the use of sodium-glucose-cotransporter-2 inhibitors (SGLT2-i)1, this medication class has gained popularity in type 2 diabetes management. However, development of euglycaemic diabetic ketoacidosis (DKA) is a concerning severe adverse effect.2 We report the case of a patient with newly diagnosed type 2 diabetes developing euglycaemic DKA (euDKA) within 3 days of commencing SGLT2-i therapy.

Case History:

A 56 years old male presented to his GP with 2 weeks of nausea, vomiting, polydipsia, weight loss. Blood tests showed a fasting BGL of 27mmol/L, HbA1c 12%, and HCO3 24mmol/L (normal range 22 – 32). Metformin, Alogliptin and Empagliflozin were simultaneously commenced. On day 3 of medication use, he presented to Emergency and was found to have euDKA, pH 7.30, pCO2 23mmHg, HCO3 11mmol/L, ketones 6.5mmol/L, lactate 1.02mmol/L and blood glucose level (BGL) 11.4mmol/L. The patient was managed in ICU with intravenous insulin infusion and rehydration. with resolution of euDKA and abdominal symptoms after 15hours. Patient was then commenced basal bolus insulin with cessation of oral hypoglycaemic agents.

Discussion:

Our patient’s gastrointestinal symptoms predisposed him to a ketosis-prone state, yet his endogenous insulin secretion initially prevented acidosis despite hyperglycaemia. The use of SGLT2-i increased urinary glucose excretion effectively decreasing BGL, yet detrimentally decreased the stimulation for physiological insulin secretion, thus promoting lipolysis and ketogenesis3. The upregulation of glucagon secretion by SGLT2-i further perpetuates fatty acid oxidation, leading to euDKA, a state of homeostatic decompensation.

Conclusion:

Though rare, euDKA is a severe adverse effect of SGLT2-i therapy which can develop within 72hours of use, with increased risk in acute physiological stress. It should not be commenced in settings of catabolic state such as acute illness or prolonged carbohydrate deprivation. Clinicians need to be vigilant of euDKA in patients presenting with acute illness whilst on SGLT2-i therapy.

  1. Zinman, Bernard, et al. "Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes." New England Journal of Medicine 373.22 (2015): 2117-2128.
  2. Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm, accessed 26th May 2017
  3. Rosenstock, Julio, and Ele Ferrannini. "Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors." Diabetes Care 38.9 (2015): 1638-1642.