Abstract: SA-PO0260
Semaglutide-Induced Lithium Toxicity in a Patient Being Treated for CKD
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Arriola Montenegro, Jose J, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
- Ordaya Gonzales, Karina M, Universidad Cientifica del Sur Facultad de Ciencias de la Salud, Miraflores, Lima, Peru
- Thongprayoon, Charat, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
- Cheungpasitporn, Wisit, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
Introduction
Semaglutide, a GLP-1 receptor agonist approved for T2DM and obesity, enhances insulin secretion, supresses glucagon, delays gastric emptying, and can induce vomiting, fluid depletion, slower GI transit, and increased oral drug absorption. Lithium, with a narrow therapeutic window and renal clearance, is sensitive to fluid shifts and altered GI motility. We report lithium toxicity induced by semaglutide in a patient on stable lithium therapy with stage 3 CKD.
Case Description
A 63 year old man with bipolar disorder (on lithium 600 mg daily for > 40 years), stage 3 CKD (baseline serum creatinine 1.64 mg/dL), T2DM, and proteinuria initiated semaglutide to address weight gain and uncontrolled diabetes/proteinuria. His pre-treatment lithium level was therapeutic at 0.9 mmol/L.Two weeks later, he presented with confusion, unsteadiness and coarse bilateral tremor of the upper limbs. Labs revealed supratherapeutic lithium level (1.8 mmol/L) and creatinine of 1.29. Poison Control recommended IV fluids and lithium level monitoring every 6 hours. Semaglutide was stopped; and the elevated lithium level was attributed to delayed gastric emptying increasing lithium absorption. With IV hydration and stopping semaglutide, lithium levels decreased from 1.8 to 1.5, and finally 0.8 mmol/L. Lithium was held until symptoms resolved and levels fell below 1.0 mmol/L. At discharge, lithium level was resumed at 300 mg daily with therapeutic lithium concentration (0.8 mmol/L). At outpatient follow up, he remains asymptomatic, with stable lithium levels.
Discussion
This case presents an interaction between semaglutide and lithium, where lithium toxicity occurred shortly after initiating semaglutide, despite a decrease in creatinine levels. The mechanism involves delayed gastric emptying increasing lithium absorption, nausea-induced dehydration, and potential reduction in renal perfusion—particularly problematic in CKD patients. Clinicians should monitor lithium levels, titrate semaglutide slowly to mitigate GI symptoms, and educate patients on proper hydration and recognizing early signs of lithium toxicity. This interaction underscores that GLP-1 receptor agonists can affect lithium pharmacokinetics through delayed absorption and dehydration, even in patients with stable renal function and chronic lithium use.