Diabetic lumbosacral radiculoplexus neuropathy after glucagon-like peptide 1 receptor agonist use: a case series

Aims: Diabetic Lumbosacral Radiculoplexus Neuropathy (DLRPN) has been historically associated to immune-mediated neuropathy with a background of microvasculitis and inflammation; however, in obese individuals there can be a dual pathology due to concomitant lumbar spondyloarthropathy-mediated entrapment of spinal roots. The former presentation in the form of acute insulin neuritis (due to rapid glycaemic improvement) has been cited not infrequently in literature. But with increasing use of potent glucose lowering agents like GLP-1 Receptor Agonists (GLP-1 RAs), there appears to be new emergence of this clinically debilitating issue which could potentially be associated with a drug-mediated pathogenesis or rapid glycaemic improvement. There are few case series and I am just depicting one such small series.

Methods: This cited case series of patients with DLRPN, based on clinical presentation and diagnostic workup, who had been exposed toGLP-1 RA’s prior to symptom onset.

Results: Six patients (3 men; aged 53–73) with type 2 diabetes developed sudden-onset, asymmetric lower limb pain followed by weakness-bilateral in 5/6. Most had substantial weight loss (35–52 lbs) and rapid HbA1c decline (>5%) in months preceding symptoms. Four patients had electrophysiological evidence of lumbosacral plexopathy; imaging of lumbosacral plexus was supportive in 2. One patient received intravenous steroids with improvement; others were managed supportively, with 3 showing stabilization or mild recovery.

Conclusions: This series highlights a potential association between rapid glycaemic and weight changes from GLP-1 RAs use and DLRPN. Clinicians should be alert to subacute neuropathy with muscle weakness in patients undergoing aggressive glycaemic control.

Comments: The reason for bringing this study up is more related to clinical practice rather than research finding. Traditionally, we have witnessed acute insulin neuritis - now called "treatment induced neuropathy of diabetes" (TIND) - mediated by rapid glycaemic reversal (historically induced by aggressive insulin usage) as a form of small fibre neuropathy with severe lancinating bilateral lower limb pain with gradual resolution over 6-9 months. But now with wider use of potent GLP-1 RAs, clinicians should be aware of this atypical form of DLRPN potentially associated with rapid glycaemic control and/or weight loss. I have personally seen 3 patients of varying severity but am not sure the evidence base for use of steroids. Physiotherapy and back-strengthening exercises did suffice in these cases. Another retrospective series (Triplett JD et al Neurology. 2025;105(3):e213916) documents an association of GLP-1-RAs with DLRPN (odds ratio 1.5) as well as common fibular neuropathy (odds ratio 1.3) but the latter could also be related to the sarcopenia associated with GLP-RAs.

Further research is needed to prospectively evaluate the risk of peripheral neurological complications from rapid glycaemic control or weight loss with GLP-1RAs, otherwise considered to have neuroprotective properties.

Sanjeev Sharma

Reference. Chandrashekhar S, Davalos L, Pradhan R, Paul P. Diabetic lumbosacral radiculoplexus neuropathy after glucagon-like peptide 1 receptor agonist use: A case series. J Neurol Sci. 2026 Jan 9;481:125755. doi: 10.1016/j.jns.2026.125755. Epub ahead of print. PMID: 41534440.

🔗 https://www.jns-journal.com/article/S0022-510X(26)00036-5/abstract