Table 1 — Common Symptoms of Diabetic Peripheral Neuropathy1

• Neuropathic pain
• Tingling
• Aching
• Numbness
• Weakness of limbs
• Burning
• Hyperalgesia and allodynia in the feet
• Sleep deprivation
• Depression


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Table 2 — Summary of Meta-Analysis Results1

Intervention

Evidence

α-lipoic acid (ALA)

• Six studies total compared 600mg ALA once daily to placebo
    o 1 study had high risk of bias (patients were pre-treated with an antidepressant)
• Five studies found significant improvements in TSS in ALA group; 1 study found improvement in TSS in placebo group
• Four studies found IV ALA significantly reduced TSS
    o Pooled analysis indicated a mean difference of -2.45 (95% CI -4.52, -0.39)
    o Substantial heterogeneity among studies
• Two studies found oral ALA significantly reduced TSS
    o Pooled analysis: mean difference of -1.95 (95% CI -2.89, -1.01)
• ALADIN III study: no significant reduction in same primary outcome after IV treatment versus oral ALA
• Conclusions
    o 600mg of oral or IV ALA once daily significantly reduce symptom scores
    o Lower doses of ALA do not decrease symptom scores

Botulinum toxin A

• Two studies total compared botulinum toxin A to placebo
    o Analyzed reduction in pain using pain scales
    o Pooled analysis: mean difference of -0.8 (95% CI -1.3, -0.4)

• Conclusions
    o Botulinum toxin A significantly reduces pain versus placebo

Monochromatic Infrared Energy (MIRE)

• Three studies total compared MIRE to placebo
    o One study: no improvement in sensation and increased risk of AEs (wounds, superficial burns, myocardial infarction)
    o One study: MIRE associated with significant benefit in pain reduction
    o One study: no significant differences between MIRE and placebo

• Conclusions
    o There is mixed evidence regarding the use of MIRE for diabetic peripheral neuropathy

Active analgesic controlled-release oxycodone, gabapentin enacarbil, clonidine gel, magnetic foot insoles, transcutaneous electrical stimulation

• Eleven studies total compared interventions to placebo
    o All studies found intervention had beneficial effects on diabetic peripheral neuropathy
    o Six of the 11 studies did not have statistically significant results
• Gabapentin enacarbil: no dose-response relationship found with different dosages

Lipo-PGE, EMLA cream, ISDN topical spray

• Three small studies total found positive effect of intervention on diabetic peripheral neuropathy symptoms
    o Standardized differences could not be calculated due to lack of data

Reflexology of the feet

• One study analyzed reflexology compared to pharmacological treatment
    o Reflexology associated with positive effects on diabetic peripheral neuropathy symptoms

Thai foot massage

• One study analyzed Thai foot massage compared to health education
    o Thai foot massage associated with positive effects on diabetic peripheral neuropathy symptoms

300mg Ponalrestat ICI 128436, 2400mg gabapentin enacarbil, pregabalin, QR-333 topical compound, micronutrients, photo stimulation 870 nm, surgical decompression

• Studies found no beneficial effect of intervention on diabetic peripheral neuropathy symptoms

Abbreviations: AEs – adverse events; ISDN – isosorbide dinitrate; IV – intravenous; TSS – total symptom score