Introduction: Diabetic peripheral neuropathy (DPN) affects approximately half of the 500 million people with type 2 diabetes worldwide. Previous studies have suggested glucagon-like peptide-1 (GLP-1) receptors in the peripheral nervous system may be a suitable target for DPN treatment.
Methods: 14 participants were consecutively recruited after being prescribed either semaglutide or dulaglutide as part of standard clinical care for type 2 diabetes. Participants underwent clinical assessment, nerve conduction studies and axonal excitability assessment at baseline and at 3 months following commencement of GLP-1 receptor agonist (GLP-1RA) therapy. This data was combined with 10 participants who had previously received exenatide therapy, and mathematical modelling of excitability data was undertaken.
Results: Clinical neuropathy scores improved at 3 months following commencement of GLP-1 (baseline TNS 3.7 ± 4.5, post-treatment TNS 2.3 ± 3.4, p=0.005). Nerve conduction studies demonstrated an improvement in sural amplitude at 3 months (baseline 11.9 ± 8.5 uV, post-treatment 14.2 ± 9.2 uV; p=0.013). Axonal excitability studies revealed changes consistent with improvements in Na+/K+ -ATPase pump function and Na+ permeability, and this was supported by mathematical modelling.
Conclusion: GLP-1RA therapy improves clinical and neurophysiological outcomes in DPN. Treatment with GLP-1RA may reverse axonal dysfunction by improving Na+/K+ -ATPase pump function.
Keywords: diabetes; glucagon-like peptide-1; glucagon-like peptide-1 receptor agonist; peripheral nerve; peripheral neuropathy.