Inflammatory bowel disease associated with the combination treatment of nivolumab and metformin: data from the FDA adverse event reporting system

PurposePD-1/PD-L1 inhibitors have demonstrated unparalleled therapeutic efficacy in multiple tumor types. Additionally, metformin has been linked to favorable outcomes in tumors. Many researchers have reported immune-mediated adverse events induced by immune checkpoint inhibitors (ICI) single agent. However, little is documented on the adverse events of the combined use of ICI and metformin.MethodsTo address this question, we used the Food and Drug Administration Adverse Event Reporting System (FAERS) to display the landscape of adverse events associated with the combined use of ICI and metformin. We identified 38 adverse event cases about the combination treatment between January 1, 2015 and June 30, 2018.ResultsThere are 36 cases in patients receiving nivolumab plus metformin (NM) therapy, and the other 2 cases were pembrolizumab plus metformin (PM). Among the 36 patients receiving NM therapy, the most common indication was for treatment of malignant lung cancer (20, 55.56%), Notably, 9 cases of inflammatory bowel disease (IBD) and diarrhea were reported.ConclusionsOur findings revealed that higher risk of IBD might occur in lung cancer patients during the combined therapy of nivolumab plus metformin. Further studies are needed to verify our findings.