Adverse events of concomitant use of immune checkpoint inhibitors and metformin or statin: an observational, retrospective disproportionality analysis

Preclinical investigations have indicated that the concurrent administration of ICIs with statins or metformin may enhance the anticancer properties. Nevertheless, the patterns of potential toxicity associated with this combination have yet to be elucidated. We utilized the Food and Drug Administration Adverse Event Reporting System (FAERS) to provide an overview of the adverse event landscape tied to the concomitant utilization of ICI and statins or metformin. Our study reveals significant side effects associated with combining ICIs with metformin or statins, including gastrointestinal, respiratory, hepatobiliary, and renal disorders. Amalgamated treatment of ICIs plus metformin may heighten the likelihood of bone marrow aplasia, inflammatory bowel disease, intestinal perforation, hepatic impairments, insomnia, autoimmune nephritis, and eczematous manifestations. For ICIs plus statins, colitis, pneumonitis, interstitial lung disease, hypothyroidism, adrenal insufficiency, myocarditis, myositis, hypophysitis, myasthenia gravis, and hepatitis. Importantly, a significant number of adverse events occur within the first two months of starting ICIs alongside metformin or statins, with some appearing after a year of treatment, emphasizing the need for ongoing monitoring. The observations delineated offer pivotal insights into the refinement of the co-administration strategy for ICIs with metformin or statins, attenuating the incidence of adverse side effects.