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

28/09/2026

AI Summary

Tirzepatide initiation in 23 lithium-treated adults produced no significant 12-week change in creatinine or eGFR, but lithium levels rose slightly (mean +0.08 mmol/L, p=0.03).
At 12 months (n=20) weight fell 17.7%, creatinine decreased and indexed eGFR rose, yet two patients had lithium >1.2 mmol/L; one required discontinuation.
No KDIGO-defined acute kidney injury confirmed; study advises structured monitoring and sick-day education; creatinine-based eGFR changes do not establish renal benefit.

Hum Psychopharmacol. 2026 Nov;41(6):e70066. doi: 10.1002/hup.70066.

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 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.

PMID:42803597 | DOI:10.1002/hup.70066

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