Glucagon-like peptide-1 receptor agonist treatment is associated with lower frequency of diabetic peripheral neuropathy and neuropathic pain in type 2 diabetes

: In this cross-sectional study, we investigated the frequency of diabetic peripheral neuropathy (DPN) and DPN-related neuropathic pain (painful DPN) in 500 consecutively enrolled patients with type 2 diabetes mellitus receiving standard treatment (n = 208), sodium-glucose cotransporter-2 inhibitors (SGLT2i; n = 152), or glucagon-like peptide-1 receptor agonists (GLP-1 RAs; n = 140). DPN was assessed through neurological examination, nerve conduction study, and skin biopsy when indicated; painful DPN was diagnosed using the grading system for neuropathic pain. Neuropathy severity and pain intensity were quantified with the Toronto Clinical Neuropathy Score, Pain Numerical Rating Scale, and Neuropathic Pain Symptom Inventory. The overall frequency of DPN was 58.6%, and painful DPN occurred in 26.2% of patients. GLP-1 RA treatment was associated with a lower frequency of DPN (46.4% vs 60.6% in the standard treatment group) and painful DPN (10.1% vs 35.1% and 28.3% in the standard treatment and SGLT2i groups, respectively). After adjustment for clinical and metabolic covariates, GLP-1 RA treatment was independently associated with lower odds of DPN (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.37-0.96) and painful DPN (OR 0.32, 95% CI 0.15-0.65). Neuropathy severity and pain intensity were also lower in patients receiving GLP-1 RAs. GLP-1 RA treatment was associated with a reduced frequency and severity of both DPN and painful DPN, independent of clinical and metabolic covariates. While these findings suggest potential neuroprotective and antinociceptive effects, longitudinal studies are needed to establish causality and clarify the underlying mechanisms.