The Effects of Metformin on Cisplatin-Induced Ototoxicity in Diabetic Patients

Objective: Ototoxicity is an important side effect of cisplatin. Recent animal and in vitro studies suggest metformin may protect hearing, though human studies are lacking. We report the first retrospective clinical study exploring the effects of metformin on cisplatin-induced ototoxicity.

Study design: Retrospective case-control.

Setting: Tertiary-care center.

Methods: We reviewed all diabetic patients treated with cisplatin who were enrolled in an auditory monitoring program between January 1, 2000 and December 31, 2018. Patients were grouped according to their use of metformin at the time of chemotherapy. Demographics, oncologic diagnosis and treatment, and prior noise exposure were recorded. Audiometric thresholds were compared before and after chemotherapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Secondary measures of ototoxicity included changes in hearing using the American Speech-Language-Hearing Association (ASHA) and TUNE criteria.

Results: Seventy-two diabetic patients met the inclusion criteria. Forty-six patients had taken metformin while on chemotherapy and 26 had not. The proportion of hearing loss as defined by both, CTCAE and ASHA criteria, was more than double in the metformin group relative to the nonmetformin group (CTCAE: 54.4% vs 19.2%, P = .004; ASHA: 62.2% vs 28.0%, P = .003). None of the potential covariates believed to be confounders were significantly associated with the outcome of multivariable analysis.

Conclusion: Contrary to expectations from preclinical data, metformin did not reduce the incidence of hearing loss in patients receiving cisplatin and may, in fact, be associated with an increased risk.