Comprehensive insights into diabetic peripheral neuropathy: pathophysiology and therapeutic approaches

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes, resulting from prolonged hyperglycemia-induced peripheral nerve dysfunction. It leads to neuropathic pain, sensory impairment, and diminished quality of life.

This review summarizes the current literature available on the pathophysiology and treatment approaches for DPN. The literature search was performed in PubMed, ScienceDirect, Scopus, and Web of Science for articles published between 2009 and 2025. The search used keywords such as "Diabetic Peripheral Neuropathy," "pathophysiology," "pharmacological treatments," and "non-pharmacological treatments." Relevant data were collected from peer-reviewed journals, clinical trials, and authoritative databases. Only studies published in English were included. Studies limited to animal models or addressing other complications of diabetes were excluded.

The pathogenesis of diabetic peripheral neuropathy is driven by metabolic and inflammatory changes that contribute to nerve damage and neuropathic pain. The United States Food and Drug Administration has approved pharmacological treatments for painful diabetic peripheral neuropathy: pregabalin, duloxetine, gabapentin, extended-release tapentadol, tramadol, and the capsaicin 8% patch. Non-Food and Drug Administration-approved therapies, such as amitriptyline and the 5% lidocaine patch, are also widely used. Non-pharmacological interventions, including tonic spinal cord stimulation, transcutaneous electrical nerve stimulation, manual acupuncture, local plantar vibration, and the Frequency Rhythmic Electrical Modulated System, show promise in alleviating symptoms and promoting nerve regeneration.

A multifaceted approach incorporating pharmacological and non-pharmacological therapies is essential for optimizing patient outcomes in diabetic peripheral neuropathy. Targeting underlying pathophysiological mechanisms while providing symptomatic relief can enhance treatment efficacy and improve the quality of life for individuals with diabetic peripheral neuropathy.