Pharmacological Management of Diabetic Neuropathy: Current Evidence, Clinical Positioning, and Emerging Therapeutic Targets.

BACKGROUND: Diabetic neuropathy is one of the most serious complications of diabetes mellitus, which is associated with pain, loss of sensation, and numbness in the extremities. Several cellular triggers, such as oxidative stress, inflammation, and glycation products, all cause nerve damage. These changes affect quality of life and may cause ulcers or amputations, so effective management is essential. OBJECTIVES: This review is conducted to identify and summarize the main pharmacological strategies that are used in the treatment of diabetic neuropathy, both the approved treatments and those that are currently under research. METHODS: This review was conducted by searching scientific databases and repositories, including Google Scholar, PubMed, and DOAJ, using keywords such as diabetic neuropathy, pharmacological treatment of pain, and antidepressant. After excluding articles, the final number of articles included in our study was approximately 107, comprising clinical studies and review articles. RESULTS: Tricyclic antidepressants as well as serotonin-norepinephrine reuptake inhibitors have been proven to help with neuropathic pain but can be associated with sedation or gastrointestinal side effects. The anticonvulsants, including pregabalin and gabapentin, decrease neuronal excitability and are reliable in reducing pain. Local therapies, such as capsaicin and lidocaine, are more local and less systemic. Opioids are also used in the treatment of recalcitrant cases due to risks of tolerance and dependence. Other recent alternatives, such as alpha-lipoic acid and erythropoietin, show promise for antioxidant and neuroprotective effects. DISCUSSION: In addition to traditionally approved medications, several drugs were tested as promising treatments. One of them is suzetrigine (VX548), which reduces pain and is recognized as a potential none opioid option. Engensis (VM202) also has clinical benefits. Acetyl-L-carnitine and Cibinetide (ara290) also show improvement in the Neuropathic score; other treatments, such as Nicotinamide riboside, after long-term use, were associated with symptomatic relief of pain. CONCLUSION: Managing diabetic neuropathy necessitates personalized treatment that equilibrates analgesia with tolerability. Current medications primarily alleviate symptoms; however, ongoing investigations into antioxidant and neuroprotective agents present the potential for therapies that may decelerate or reverse nerve damage.