Table 1: Therapeutic interventions for diabetic polyneuropathy.
| Therapy | Evidence |
|---|---|
| Disease control | |
| α-lipoic acid | A 2004 meta-analysis of four trials (n=1,258) concluded that treatment with α-lipoic acid (600 mg/day IV) over 3 weeks is safe and gives clinically meaningful improvements in both positive neuropathic symptoms and neuropathic deficits in patients with symptomatic DPN45 |
| Benfotiamine | Phase III study (n=181) showed modest improvements in NSS but not TSS46 |
| Metanx® | Phase III study (n=214) showed no significant effect on VPT but significant improvement in NTSS-6 scores47 |
| Vitamin D | Recent study showed reduced vitamin D levels in patients with painful DPN. No intervention trials have been conducted yet48 |
| Epalrestat | An open-label study (n=109) found that epalrestat was shown to suppress onset/progression of both diabetic neuropathy and diabetic retinopathy/nephropathy over a 3-year period49 |
| Pain control | |
| Tricyclic antidepressants | A number of RCTs have suggested efficacy50 |
| Serotonin-norepinephrine reuptake inhibitors | Duloxetine was the first medication to be approved specifically for the treatment of DPN and its use is supported by data from three RCTs51–3 |
| γ-aminobutyric acid analogues | Pregabalin is FDA approved;54 there is mixed evidence for gabapentin;55 mirogabalin received approval in Japan after causing significant reductions in DPN pain in a phase II trial56 |
| Opioids (morphine sulphate, oxycodone) | Established use in chronic pain.57 Risks in relation to opioid misuse, abuse and addiction |
| Oxacarbezine | A phenotype-stratified RCT (n=83) found oxacarbezine was not beneficial in non-irritable nociceptor phenotype but was effective in irritable-nociceptor phenotype58 |
| Lidocaine 5% patch | Only approved for patients with postherpetic neuralgia59 |
| Capsaicin 8% patch | Approved in Europe for use in DPN60 |
IV = intravenous; DPN = diabetic polyneuropathy; NSS = Neuropathy Symptom Score; NTSS-6 = Neuropathy Total Symptom Score-6; RCT = randomised controlled trial; TSS = Total Symptom Score; VPT = vibrational perception threshold.