What are the first-line treatments for diabetic neuropathy?

From the Guidelines

First-line treatments for diabetic neuropathy should prioritize gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers as initial pharmacologic treatments for neuropathic pain in diabetes, as recommended by the most recent guidelines 1.

Key Considerations

• Optimal glycemic control is fundamental to prevent progression of nerve damage, aiming for HbA1c levels below 7% 1.
• For pain management, medications such as pregabalin, gabapentin, and duloxetine are considered first-line treatments due to their efficacy in modulating pain signals in the nervous system 1.
• Treatment should be individualized based on comorbidities, potential side effects, and patient preference, with consideration of regular foot care, physical therapy, and exercise to maintain function and reduce pain 1.

Medication Options

• Gabapentinoids: pregabalin (starting at 50mg three times daily, maximum 600mg/day) or gabapentin (starting at 300mg daily, gradually increasing to 1800-3600mg/day in divided doses) 1.
• Serotonin-norepinephrine reuptake inhibitors: duloxetine (60-120mg daily) 1.
• Tricyclic antidepressants: amitriptyline (10-25mg at bedtime, increasing to 25-100mg if needed), though may have more side effects in older patients 1.
• Sodium channel blockers: may be considered for treating pain in DPN, with options including lamotrigine, lacosamide, oxcarbazepine, and valproic acid 1.

Important Considerations

• Opioids, including tramadol and tapentadol, should not be used for neuropathic pain treatment in diabetes due to the potential for adverse events 1.
• Concurrent treatment of sleep and mood disorders is recommended due to their increased frequency in individuals with diabetic peripheral neuropathy 1.

From the FDA Drug Label

14.4 Diabetic Peripheral Neuropathic Pain in Adults The efficacy of duloxetine delayed-release capsules for the management of neuropathic pain associated with diabetic peripheral neuropathy in adults was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose trials in adult patients having diabetic peripheral neuropathic pain (DPNP) for at least 6 months (Study DPNP-1 and Study DPNP-2).

First-line treatments for diabetic neuropathy include duloxetine delayed-release capsules.

• The recommended dose is 60 mg once daily or 60 mg twice daily.
• Treatment with duloxetine delayed-release capsules statistically significantly improved the endpoint mean pain scores from baseline and increased the proportion of patients with at least a 50% reduction in pain scores from baseline 2.
• Key benefits of duloxetine delayed-release capsules for diabetic neuropathy include improved pain management and increased proportion of patients with at least a 50% reduction in pain scores.
• Important considerations for patients with diabetes include the potential for worsened glycemic control, as observed in DPNP trials 2.

From the Research

First-Line Treatments for Diabetic Neuropathy

• Anticonvulsants like pregabalin and gabapentin are the preferred first-line treatment for diabetic peripheral neuropathy (DPN) 3
• Amitriptyline, duloxetine, and venlafaxine are also considered first-line treatments for DPN 3
• These medications are recommended for pain management in DPN, with studies showing significant pain reduction in patients treated with these drugs 4, 5, 6

Comparison of First-Line Treatments

• A comparative study found that amitriptyline, pregabalin, and duloxetine were all effective in reducing pain in patients with painful diabetic peripheral neuropathy, with amitriptyline showing more favorable findings 4
• Pregabalin is a first-line treatment in all major international guidelines on the management of painful diabetic neuropathy (pDPN) and has been shown to lead to a clinically meaningful improvement in pain scores 5

Additional Treatment Options

• Topical agents like capsaicin and isosorbide dinitrate may be considered for second or third-line treatment of DPN 3
• Opioids and related drugs are suggested for short-term use during the acute exacerbation of pain, but are not recommended for long-term use due to the risk of dependence and other side effects 3
• Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) may also be effective in reducing pain in patients with diabetic neuropathy 6, 7