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Tirzepatide Initiation in Lithium-Treated Bipolar Disorder: Renal Biomarker Trajectories and Lithium Safety Signals
Maria Beatrice Rescalli1, Andrea Fagiolini1, Pietro Carmellini1
1Division of Psychiatry, Department of Molecular Medicine, University of Siena School of Medicine, Siena, Italy.
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 m2 (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 m2 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.
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