GLP-1RA–Associated Diabetic Lumbosacral Radiculoplexus and Common Fibular Neuropathies

BACKGROUND AND OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to treat obesity and diabetes. Semaglutide, a GLP-1RA, is linked to nonarteritic ischemic optic neuropathy (NAION), macular edema, and retinopathy. Because diabetic lumbosacral radiculoplexus neuropathy (DLRPN) and common fibular neuropathy (CFN) are associated with weight loss, we examined whether GLP-1RA usage is linked to these neuropathies. METHODS: We conducted a retrospective case-controlled study from April 28, 2005 (the first GLP-1RA Food and Drug Administration approval), to December 25, 2024. Patients diagnosed with DLRPN or CFN were analyzed for GLP-1RA exposure and clinical characteristics. A control group, matched for age, sex, body mass index (BMI), and diabetes status, was used to assess for an association with GLP-1RA use. RESULTS: = 0.018). All episodes occurred after 2015, with 3 DLRPN events and 7 CFN events occurring between 2015 and 2019, rising to 24 and 70 cases in 2020-2024, reflecting increases of 700% and 900%. DISCUSSION: GLP-1RA use is associated with an increased likelihood of DLRPN and CFN. DLRPN and its associated nerve microvasculitis seem more strongly linked to metabolic changes, particularly significant HbA1c reductions, while CFN has compressive neuropathy characteristics and is more influenced by weight loss.