Semaglutide and Lithium Carbonate: Interaction Details

a) A 62-year-old man with a history of bipolar I disorder presented with altered mental status, worsening fatigue, dizziness, and worsening tremors. He had been psychiatrically stable for 4 decades on lithium carbonate, 600 mg ER daily for the last 6 years. His lithium level on admission was 1.8 mmol/L; all other tests were unremarkable. Previous steady-state lithium levels were 1 mmol/L 6 months before admission and 0.9 mmol/L 18 months before admission. He received 2 doses of semaglutide 0.25 mg SUBQ weekly 2 to 3 weeks prior to presentation. Lithium and semaglutide were discontinued, and he was started on IV fluid hydration, resulting in a steady decline in lithium levels: 1.5 mmol/L at 6 hours, 1.3 mmol/L at 12 hours, 1 mmol/L at 24 hours, and 0.8 mmol/L at 36 hours, accompanied by gradual improvement in mental status. A 23-year-old woman with bipolar I disorder and borderline personality disorder was admitted to the hospital for lithium toxicity. She was taking lithium carbonate ER 900 mg in addition to multiple other psychiatric medications and an unreliable history of semaglutide use. Presenting symptoms included dizziness, abdominal pain, tremors, visual disturbances, speech changes, nausea, vomiting, and decreased appetite. The patient’s lithium level on admission was 2.1 mmol/L. Lithium and semaglutide were discontinued. After 4 days, the lithium level had decreased to 0.5 mmol/L. Baseline renal function, hydration status, and lithium levels should be assessed before initiating semaglutide, and monitoring of lithium levels frequently during concomitant therapy is recommended ¹.

b) A 41-year-old woman with a history of major depressive disorder, posttraumatic stress disorder, generalized anxiety disorder, borderline personality disorder, body dysmorphic disorder, unspecified eating disorder, obesity, and stage 2 chronic kidney disease initiated lithium therapy with extended-release 300 mg orally twice daily and gradually titrated to 600 mg orally twice daily over 7 months. Two weeks after the final dose increase, her lithium level was 1.1 mEq/L, and her creatinine was 1.16 mg/dL; she remained therapeutic for nearly 1 year. Approximately 2 years after starting lithium, she initiated semaglutide 0.25 mg SUBQ once weekly for weight management. One week later, the patient started to develop nausea, tremulousness, gait disturbance, muscle twitching, shakiness, dizziness, and irritability. Laboratory testing 5 weeks after initiating semaglutide confirmed lithium toxicity. Laboratory results included lithium level of 2.4 mEq/L and creatinine of 1.09 mg/dL. The patient was managed conservatively by discontinuing lithium and increasing hydration while continuing semaglutide. One day after stopping lithium, laboratory testing showed a decrease in the lithium level of 2.2 mEq/L and a further decrease to 1.2 mEq/L 3 days after stopping therapy. The patient was restarted on lithium at half of her original dose, 300 mg twice daily, along with 0.25 mg weekly SUBQ semaglutide. Follow-up laboratory tests at 6 and 32 days after restarting therapy showed stable therapeutic lithium levels of 0.9 and 0.8 mEq/L, respectively ².