Association of Hypoglycemic Agents with the Risk of Platinum-Based Chemotherapy-Induced Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION

In patients with cancer who also have type 2 diabetes (T2D), platinum-based chemotherapy can worsen the neuropathy owing to its neurotoxicity. 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-potentially (CIPN-P) has not been fully validated, and which drugs are associated with a decreased incidence of neuropathy in this context remains unclear.

METHODS

We conducted a retrospective cohort study by using the nationwide Medical Data Vision claims database in Japan, which includes patients treated at acute-care hospitals. From April 2008 to December 2022, 119,061 patients with T2D were prescribed hypoglycemic agents and received platinum-based chemotherapy. Patients with type 1 diabetes, other diabetes types, or pre-existing neuropathy were excluded. The outcome, CIPN-P, was defined as a new prescription of gabapentin, duloxetine, mirogabalin, pregabalin, or cyanocobalamin following an International Classification of Diseases, 10th Revision code for peripheral neuropathy. Patients were followed for 3 years after chemotherapy. Baseline covariates included age, sex, body mass index, hemoglobin A1c, and estimated glomerular filtration rate. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We examined their diagnoses, treatments, and procedures, categorizing them into patients with CIPN-P (n = 22,559) and those without (n = 96,502).

RESULTS

The incidence of CIPN-P was 18.9%. The concomitant use of sodium-glucose cotransporter 2 inhibitors was associated with a lower risk of CIPN-P, with an overall HR of 0.89 (95% CI: 0.82-0.96, p = 0.01). Empagliflozin (HR: 0.85) and dapagliflozin (HR: 0.85) were each associated with a significantly lower risk.

CONCLUSION

These results suggest that sodium-glucose cotransporter 2 inhibitors may be associated with a lower risk of CIPN-P in patients undergoing platinum-based chemotherapy. These associations may support more individualized antidiabetic treatment strategies in patients receiving platinum-based chemotherapy.