Empagliflozin-Mediated Lithium Excretion: A Case Study and Clinical Applications

Patient: Male, 30-year-old Final Diagnosis: Schizoaffective disorder Symptoms: Renal excretion of lithium Medication: Empagliflozin Clinical Procedure: — Specialty: Nephrology • Psychiatry OBJECTIVE: Unusual or unexpected effect of treatment BACKGROUND: Empagliflozin selectively reduces apical sodium-glucose co-transporter 2 function in the proximal convoluted tubules, increasing sodium and glucose excretion in the urine, ultimately reducing glucose reabsorption in the kidneys for diabetic management. Lithium, the gold-standard treatment for bipolar disorder, also utilizes sodium transporters in the proximal convoluted tubules. CASE REPORT: Presenting with a manic relapse of refractory schizoaffective disorder, our patient was found to have subtherapeutic levels of lithium on admission due to poor outpatient medication compliance. Restoration to therapeutic lithium levels allowed inpatient blood glucose measurements, which led to a new diagnosis of type 2 diabetes mellitus. Given his comorbid severe hepatic impairment, obesity, and prior pancreatitis, the patient was started on empagliflozin to safely manage this new diagnosis without collateral organ injury. Routine monitoring found reproducible and clinically significant decreases in serum lithium levels in the presence of empagliflozin therapy, without obvious confounding factors. Subsequent discussion with specialist teams resulted in trialling metformin, which adequately controlled the new diabetic diagnosis without inpatient complications. CONCLUSIONS: We suspect that empagliflozin reduced sodium-glucose and lithium-glucose reabsorption in the proximal connecting tubules, thereby increasing the renal excretion of sodium, glucose, and lithium. Applications include awareness of the interaction between these medications, support for the role of physiological SGLT-2-mediated lithium transport, and the possibility of using empagliflozin and other SGLT-2 inhibitors to treat life-threatening lithium toxicity.