Association of hypoglycemic agents with the risk of platinum-based chemotherapy-induced peripheral neuropathy in patients with type 2 diabetes mellitus

In patients with cancer who also have type 2 diabetes, platinum-based chemotherapy can worsen the neuropathy owing to its neurotoxic effects. Novel glucose-lowering agents may mitigate chemotherapy-induced peripheral neuropathy by improving glycemic control and reducing metabolic stress. However, their clinical utility in reducing the risk of chemotherapy-induced peripheral neuropathy has not been fully validated, and which specific glucose-lowering drugs are associated with a decreased incidence of neuropathy in this context remains unclear. In this retrospective cohort study, we included 119,061 patients with type 2 diabetes who received platinum-based chemotherapy, with data captured from April 2008 to December 2022 in Japan’s Medical Data Vision database We examined their diagnoses, treatments, and procedures, categorizing them into patients with chemotherapy-induced peripheral neuropathy-potentially (n = 22,559) and those without (n = 96,502). The incidence of chemotherapy-induced peripheral neuropathy-potentially was 18.9%. The concomitant use of sodium–glucose cotransporter 2 inhibitors was associated with a significantly lower risk of chemotherapy-induced peripheral neuropathy-potentially, with an overall hazard ratio of 0.89 (95% confidence interval: 0.82–0.96). Empagliflozin (hazard ratio: 0.85) and dapagliflozin (hazard ratio: 0.85) were each associated with a significantly lower risk. These results suggest that sodium–glucose cotransporter 2 inhibitors may mitigate chemotherapy-induced peripheral neuropathy-potentially in patients undergoing platinum-based chemotherapy.