Objective:

To report a case series of Diabetic Lumbosacral Radiculoplexus Neuropathy (DLSRPN) in association with Glucagon-Like Peptide-1(GLP-1) analog.  

Background:

DLSRPN, a rare form of diabetic neuropathy is a subacute, usually painful, asymmetric, motor-predominant, non-length dependent lower limb neuropathy associated with muscle weakness and atrophy, rarely progressing to paraplegia.  Risk factors include rapid or tight glycemic control. GLP-1 analogs are increasingly popular in managing diabetes mellitus (DM) due to their superior efficacy in blood glucose control, weight management, and purported cardioprotective benefits. Their effects on diabetic neuropathy remain unknown.

Design/Methods:

We report 3 cases of DLSRPN in association with GLP-1 analog use.  

Results:

Three male patients (aged 59-73 years) with type 2 DM (one newly diagnosed), treated with GLP-1 analogs, presented with acute-onset neuropathic pain followed by asymmetric leg weakness—bilateral in two and unilateral in one. All reported significant weight loss (20-40 lbs) over 3-4 months around onset of symptoms. Examination revealed asymmetric lower limb sensorimotor deficits and muscle atrophy, with two patients showing severe weakness and sharp drop in HbA1c (>4%). Extensive investigations for an alternative etiology were unremarkable. Imaging and electrodiagnostics in one patient confirmed asymmetric lumbosacral plexopathy and he was treated with intravenous steroids. The other two received supportive care; all three experienced symptom stabilization and gradual improvement.

Conclusions:

These cases highlight the risk of DLSRPN associated with GLP-1 analogs. In meta-analyses, long-acting GLP-1 analogs result in greater A1C reductions, with semaglutide leading to the largest change. Weight loss ranges from 5 to 20% depending on the drug and dose. The striking efficacy and unpredictable rate of change in weight and A1c may pose a risk for this rare diabetic complication. Clinicians should remain vigilant for signs of subacute motor-predominant neuropathy, especially in patients with rapid HbA1c reductions. Further research is needed to explore the effects of GLP-1 analogs on diabetic neuropathy.