SUN-699 Canagliflozin Induced Severe Hyponatremia- a Rare Life Threatening and Poorly Understood Complication- a Case Report

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load. This can occasionally lead to severe dehydration, hypotension and in some cases, severe hyponatremia. The effects of SGLT2 inhibitors on sodium and water handling by the renal tubules is not well studied. Clinical Case: A 49-year-old male with history of type 2 diabetes mellitus on canagliflozin, an SGLT2 inhibitor, who was brought to the Emergency Room following a motor vehicle accident from acute onset of confusion and altered mental status. Initial trauma workup was negative. He was found to have severe hyponatremia to 118 mEq/ L (n 135–145 mEq/ L) and was also noted to be in euglycemic ketoacidosis with positive serum ketones (qualitative assessment) along with acute onset urinary retention. Urine toxicology was negative including negative blood alcohol level. Thyroid function was normal 1.080 mIU/ L (n 0.47- 6.90mIU/L). His total urine osmolar excretion was ~ 2400 mOsm in 12h (n 500–800 mOsm/kg of water/ 24 hours), confirming the diagnosis of his ongoing massive osmotic diuresis. On admission, his antidiuretic hormone (ADH) level was noted to be elevated to 9.1 pg/mL (n <4.3pg/ mL). This severe degree of hyponatremia was postulated to be secondary to canagliflozin causing massive osmotic diuresis resulting in severe intravascular volume depletion with reflex increase in antidiuretic hormone (ADH) compounded by increased free water intake by the patient. Conclusion: With more widespread use of this relatively new hypoglycemic medication with protective metabolic and cardiovascular benefits that include weight loss and reduction of BP in T2DM patients, it is equally important to understand the physiology of potentially life-threatening adverse effects associated with severe volume depletion by massive osmotic diuresis and electrolyte abnormalities that include hypernatremia (even hyponatremia), and the timely recognition of euglycemic ketoacidosis.