The nephroprotective effect of metformin with cisplatin in bladder cancer: randomized clinical trial

Cisplatin-based combination chemotherapy is the mainstay treatment strategy in various forms of carcinomas and sarcomas. However, its dosage and therapeutic efficacy are significantly limited by its nephrotoxicity. Based on metformin renal benefits in different studies, the study aims to determine safety and the potential nephroprotective effect of metformin when used with cisplatin in patients with bladder cancer.

This was a prospective, randomized, parallel, controlled, open-label study in which 78 chemotherapy naïve bladder cancer patients aged 18-65 years and would receive gemcitabine/cisplatin regimen were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving cisplatin standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for four cycles of gemcitabine/cisplatin with assessment of renal function tests, serum neutrophil gelatinase-associated lipocalin (NGAL), cystatin-c, and metformin's adverse effects.

Serum creatinine, serum NGAL, and cystatin-C significantly increased in the control group only (P < 0.001). Estimated glomerular filtration rate (eGFR) significantly declines in the control group only (P < 0.001). On the contrary, serum NGAL significantly improved in the treatment group (P = 0.02) with stable and normal mean value of serum creatinine, eGFR, and cystatin-C without a concomitant significant increase in adverse events, such as hypoglycemia, gastrointestinal symptoms, or weight loss compared to the control group.

Metformin prevented renal damage and deterioration in kidney function in cisplatin-treated patients. Therefore, it is a promising agent in reducing cisplatin-induced nephrotoxicity. The study was registered in ClinicalTrials.gov on December, 16, 2023, Identifier Number NCT06215976.