From the Guidelines
Treatment for painful diabetic peripheral neuropathy should prioritize a multi-faceted approach, including optimizing glucose control, assessing and treating pain, and using first-line medications such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers, as recommended by the most recent guidelines 1.
Key Considerations
- Optimizing glucose control is essential to prevent or delay the development of neuropathy in people with type 1 diabetes and to slow the progression of neuropathy in people with type 2 diabetes 1.
- First-line medications for neuropathic pain in diabetes include gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers 1.
- Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has been shown to be effective in the treatment of pain associated with diabetic peripheral neuropathy, with doses of 60 and 120 mg/day demonstrating efficacy in multicenter randomized trials 1.
- Tapentadol, a centrally acting opioid analgesic, is not generally recommended as a first- or second-line therapy due to the high risk for addiction and safety concerns compared with the relatively modest pain reduction 1.
Treatment Options
- Anticonvulsants such as pregabalin (Lyrica) at 150-300 mg daily in divided doses or gabapentin (Neurontin) starting at 300 mg daily and titrating up to 1800-3600 mg daily in divided doses.
- Serotonin-norepinephrine reuptake inhibitors such as duloxetine (Cymbalta) at 60-120 mg daily.
- Tricyclic antidepressants such as amitriptyline at 25-100 mg at bedtime, though these have more side effects, particularly in older adults.
- Topical treatments such as capsaicin cream (0.075%) or lidocaine patches (5%) can provide localized relief with minimal systemic effects.
Additional Recommendations
- Regular foot care, including daily inspection, proper footwear, and regular podiatry visits, helps prevent complications.
- Physical therapy, transcutaneous electrical nerve stimulation (TENS), and acupuncture may provide additional relief.
- Tight glycemic control is essential to prevent progression, with target HbA1c below 7%.
From the FDA Drug Label
Pregabalin is indicated for: Management of neuropathic pain associated with diabetic peripheral neuropathy 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
Treatment Options:
- Pregabalin (PO) is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy 2
- Duloxetine (PO) is also effective in the management of neuropathic pain associated with diabetic peripheral neuropathy in adults 3
From the Research
Treatment Options for Painful Diabetic Peripheral Neuropathy
- The following medications have been found to be effective in treating painful diabetic peripheral neuropathy:
- Amitriptyline, pregabalin, and duloxetine, with amitriptyline showing more favorable findings with tolerable side effects 4
- Pregabalin has been shown to produce significant improvements in mean pain scores, sleep interference scores, and quality of life 5
- Gabapentin and amitriptyline are also considered for initial treatment, along with pregabalin and duloxetine, which are approved by the U.S. Food and Drug Administration for treating this disorder 6
- Second-line therapy includes opioid-like medications, venlafaxine, desvenlafaxine, and topical agents such as lidocaine patches and capsaicin cream 6
- Other treatment options that may provide relief include isosorbide dinitrate spray, transcutaneous electrical nerve stimulation, acupuncture, and alpha-lipoic acid, although the evidence for these is limited 6, 7
Efficacy and Safety of Treatment Options
- Pregabalin has been found to be safe and effective in decreasing pain associated with diabetic peripheral neuropathy, with significant improvements in pain scores and sleep interference scores 5, 8
- The efficacy of pregabalin is dose-related, with the greatest effect observed at a dosage of 600 mg/day 8
- Common adverse events associated with pregabalin include dizziness, somnolence, and peripheral edema 5, 8
- Amitriptyline, pregabalin, and duloxetine have been found to be associated with adequate pain reduction, although amitriptyline had more favorable findings with tolerable side effects 4
Considerations for Treatment
- Clinicians should carefully consider the patient's goals and functional status, as well as potential adverse effects of medication, when choosing a treatment for painful diabetic peripheral neuropathy 6
- Periodic, objective monitoring of medication response is critical, as patients may not obtain desired pain reduction and adverse effects are common 7
- Opioids should generally be avoided due to the risk of serious adverse effects 7