Meds for diabetes may protect the kidneys on lithium
REVIEW OF: Ercis M et al, Bipolar Disord 2026;28:e70094
STUDY TYPE: Restrospective cohort study
EVIDENCE GRADE: Low (4/10)
Background
Renal risks on lithium are the biggest drawback for this medication. There are few solutions, though dosing at night, keeping the levels below 0.8, and adding NAC may help. This Mayo Clinic study asks whether SGLT2 inhibitors, diabetes medications with known protective effects in chronic kidney disease, might also protect the kidneys on lithium.
The Trial
They tracked 56 patients with mood disorders (88% bipolar disorder) who had been on lithium for an average of seven years and later started an SGLT2 inhibitor for various reasons (mainly empagliflozin, brand Jardiance 10-25 mg daily for type 2 diabetes). The researchers compared their renal function (eGFR) before and after initiation.
Before starting the SGLT2 ihibitor, renal eGFR was declining at –1.43 mL/min/1.73m² per year. After initiation, that trajectory reversed, with a statistically significant slope change of +2.13 mL/min/1.73m² per year (p=0.025). Sensitivity analyses trended in the same direction but lost significance, possibly due to the small subgroup sizes.
Risks
Urinary infections showed up as a side effect in this study. Other known risks include increased urination, dehydration and low blood pressure (hypotension).
Reassuringly, serum lithium levels didn’t change meaningfully on the SGLT2 inhibitors, though this was measured in only 11 patients — too few to rule out a clinically relevant interaction.
Practice Implications
Although renal impairment is a real risk, lithium also has medical benefits, and patients with bipolar disorder live longer on it than with other medications. To reduce the renal risk:
- Dose entirely at night
- Keep the levels below 0.8 and avoid toxicity
- Consider N-acetylcysteine (NAC). This well-tolerated supplement has evidence in bipolar depression, and it protected the kidneys in animal models of lithium damage and in several human trials of chronic kidney disease and renal toxicity.
- Consider adding empagliflozin if eGFR declines, but this step is riskier than NAC. Monitor lithium levels closely after starting, since empagliflozin may affect lithium clearance.
- Consult nephrology if the eGFR falls below 60 mL/min/1.73m² (or creatinine above 1.5 mg/dL, but eGFR is more accurate)
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
Share Your Input in Comments
- I rarely recommend treatments based on an uncontrolled trial, but here the risk is serious and we have confirmation from non-lithium patients for NAC and SGLT2. Where do you see their role?
