Therapeutic Targets, Pharmacological Mechanisms, and Delivery Strategies for Diabetic Peripheral Neuropathy.

With the global diabetes population projected to reach 783 million by 2045, diabetic peripheral neuropathy (DPN) remains a common and debilitating complication characterized by metabolic stress, inflammation, and microvascular dysfunction. This review summarizes current interventions for DPN from the perspective of therapeutic targets, pharmacological mechanisms, and emerging delivery strategies. Conventional pharmacotherapy mainly provides symptomatic relief; first-line analgesics such as duloxetine and pregabalin offer only moderate benefit, with a number needed to treat of approximately 4-5. Natural products, including resveratrol, ginkgo biloba, and tanshinone IIA, show antioxidant and anti-inflammatory potential, although supporting evidence remains largely preclinical. Emerging targeted therapies and nanocarrier-based delivery systems may improve disease modification and drug bioavailability. Overall, DPN treatment remains limited by the lack of disease-modifying therapies, insufficient high-quality clinical evidence, and major translational barriers. Future priorities include mechanism-based stratification, combination strategies, and rigorous trials incorporating objective and patient-reported outcomes.