Diabetic peripheral neuropathy (DPN) is one of the commonest complications of diabetes mellitus (DM). Current therapeutic approaches largely focus on pain management. However, less evidence is available on the clinical potential of two widely prescribed drug categories in DM management: dipeptidyl peptidase 4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs). In this review, we discuss evidence from both experimental and clinical studies on the potential utility of these drugs in the management of DPN. Immunohistochemical data indicate that agents in both categories promote neurite outgrowth, ion conduction, neuronal survival and Schwann cell function. Furthermore, intra-epidermal nerve fibre density has been reported to increase with DPP-4is or GLP-1RAs treatment. Moreover, electrophysiological studies have indicated a diverse, but mostly beneficial, effect on motor or sensory nerve conduction velocity. Clinical tests, such as the muscular grip or paw jumping control resembling neuropathic symptoms, have also confirmed the advantageous effect of DPP-4is and GLP-1RAs. Finally, limited but promising clinical data have shown improved somatosensory-evoked potentials and vibration perception threshold, as well as restored excitability and nerve size parameters. Nevertheless, further clinical studies are required to elucidate the exact role of DPP-4is and GLP-1RAs in DPN.
