Tirzepatide Initiation in Lithium‐Treated Bipolar Disorder: Renal Biomarker Trajectories and Lithium Safety Signals Over 12 Months in a Real‐World Cohort

ABSTRACT Objective To assess early renal and lithium‐related safety and 12‐month renal biomarker trajectories after tirzepatide initiation in lithium‐treated adults with bipolar disorder. Methods We retrospectively studied 23 adults at one centre. The principal 12‐week renal safety measures were serum creatinine and derived CKD‐EPI 2021 creatinine‐based eGFR. Secondary outcomes included lithium, electrolytes, gastrointestinal symptoms, acute kidney injury meeting KDIGO creatinine criteria and discontinuation. Twelve‐month trajectories and body‐surface‐area‐unindexed eGFR were exploratory. Results At 12 weeks, creatinine changed by −3 ± 12 μmol/L ( p = 0.196), indexed eGFR by +2.6 ± 15.1 mL/min/1.73 m 2 ( p = 0.259) and lithium by +0.08 ± 0.17 mmol/L ( p = 0.030). Among 20 on‐treatment completers at 12 months, weight decreased by 17.7 ± 6.0%, creatinine by 12 ± 9 μmol/L, indexed eGFR increased by 13.0 ± 12.1 mL/min/1.73 m 2 and unindexed eGFR by 4.5 ± 14.3 mL/min. Two patients had lithium > 1.2 mmol/L; one developed clinician‐attributed symptomatic toxicity and discontinued tirzepatide. No acute kidney injury meeting KDIGO creatinine criteria could be confirmed from available records. Conclusions Co‐prescription warrants structured monitoring and sick‐day education. Creatinine‐based eGFR changes during major weight loss do not establish renal benefit or exclude kidney injury.