Glucagon-like peptide-1 receptor agonists and the risk of chemotherapy-induced peripheral neuropathy in patients with diabetes: A real-world study.

12133 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent condition that significantly affects quality of life in patients with cancer. Diabetes and the use of taxane or platinum-based chemotherapy are major risk factors for CIPN. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) have emerged as promising agents for preventing CIPN due to their potent antihyperglycemic and weight-loss effects. However, the effects of GLP-1RA on CIPN are unknown. Methods: We conducted a retrospective, propensity score-matched cohort study utilizing the TriNetX Analytics Network database. Adult patients with concurrent diagnoses of cancer and diabetes who were treated with taxane and/or platinum-based chemotherapy and either GLP-1RA or non-GLP-1RA (including Insulin, Dipeptidyl peptidase-4 inhibitors, Sodium-glucose Cotransporter-2 Inhibitors, Metformin, Thiazolidinediones) anti-diabetes agents were included. Patients with a prior history of neuropathy were excluded. The index date was defined as the initiation of chemotherapy. The primary outcome was the occurrence of CIPN, identified using International Classification of Diseases codes, within one year following the index date. Secondary outcomes included the use of neuropathic pain medications, such as gabapentinoids, serotonin and norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and tramadol. Cohorts were matched on variables such as age, race, sex, hemoglobin A1c, BMI, cancer type, metastatic disease, and underlying comorbidities. Results: We identified 39,772 patients eligible for inclusion, among which 1813 received GLP-1RA and 37,959 received non-GLP-1RA. After propensity score matching, cohorts were all well-balanced across variables. We included 1,763 patients in each cohort for the final analysis. The mean BMI for the GLP-1RA and non-GLP-1RA groups are 32.5 ± 7.5 and 32.2 ±7.7, and the mean HbA1c are 7.7 ± 1.8 and 7.6 ± 1.8, respectively. When compared with patients who received non-GLP-1RA, patients who received GLP-1RA had a higher risk of CIPN (13.9 vs 10.9%, HR 1.34 [95% CI: 1.11 - 1.62]) and significantly increased use of gabapentinoids, SNRI, and tramadol (Table). Conclusions: GLP-1RAs are associated with a higher risk of CIPN and greater use of neuropathic pain medications than non-GLP-1RA in patients with cancer and diabetes receiving taxane/platinum-based chemotherapy. Further studies are required to elucidate the possible mechanism underlying the increased risk of CIPN associated with GLP-1RAs. GLP-1RA vs. non GLP-1RAHR (95% CI) P-value Chemotherapy-induced neuropathy 1.34 (1.11 - 1.62) 0.002 Gabapentinoids (gabapentin/ pregabalin) 1.26 (1.13 - 1.41) <0.001 duloxetine 1.66 (1.30 - 2.12) <0.001 Venlafaxine 1.56 (1.09 - 2.22) 0.010 TCA 1.05 (0.69 - 1.61) 0.70 Tramadol 1.30 (1.16 - 1.54) <0.001