Benfotiamine Versus Vitamin B1-6-12 for Diabetic Peripheral Neuropathy

Inclusion Criteria:

• Age ≥18 years.
• Diagnosis of diabetic peripheral neuropathy confirmed by a physician based on the following ICD-10 codes: E11.42: Type 2 diabetes mellitus with diabetic polyneuropathy; or E11: Type 2 diabetes mellitus, combined with either:

M79.2: Neuralgia and neuritis, unspecified; or G62.9: Polyneuropathy, unspecified.

• Presence of sensory neuropathy symptoms assessed using the Neuropathy Total Symptom Score-6 (NTSS-6), with: Total NTSS-6 score ≥1; and Numbness symptom score (NTSS-6 item 6) ≥1.
• No evidence of vitamin B12 deficiency, defined as a serum vitamin B12 level ≥200 pg/mL (148 pmol/L).
• provide informed consent and participate in the study.

Exclusion Criteria:

• Presence of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltose malabsorption.
• Adjustment of doses of medications used for neuropathic pain control within 6 weeks prior to study enrollment, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, or other neuropathic pain medications.

• Presence of other conditions that may affect diabetic peripheral neuropathy or neuropathic pain, including:

  • Chemotherapy-induced peripheral neuropathy due to neurotoxic agents within 6 months prior to enrollment, including vinca alkaloids, taxanes, platinum-based agents, proteasome inhibitors, thalidomide, brentuximab vedotin, or ado-trastuzumab emtansine.
  • HIV/AIDS with any of the following: Current or previous treatment with didanosine, stavudine, or zalcitabine; CD4 count <200 cells/mm³; or HIV viral load >1,000 copies/mL.
  • Drug-induced polyneuropathy (ICD-10: G62.0).
  • Polyneuropathy due to other toxic agents (ICD-10: G62.2).
  • Alcoholic polyneuropathy (ICD-10: G62.1).
  • Fibromyalgia (ICD-10: M79.7).
  • Planned surgery within 3 months prior to or during the study period.
  • Previous pain-relief procedures, including:
• Transcutaneous electrical nerve stimulation (TENS) or temporary peripheral nerve stimulation (PNS) within 1 year prior to enrollment;
• Permanent PNS;
• Pulsed radiofrequency or radiofrequency ablation within 6 months prior to enrollment;
• Botulinum toxin injection for neuropathic pain relief within 12 weeks prior to enrollment.
• Adjustment of glucose-lowering medication doses or HbA1c >8% within 3 months prior to study enrollment.
• Pregnancy, planned pregnancy within 3 months, or currently breastfeeding.
• Inability to attend scheduled study visits in person or through telemedicine follow-up as required by the study protocol.
• Known allergy or hypersensitivity to benfotiamine or any component of benfotiamine, vitamin B1, vitamin B6, or vitamin B12.
• Previous use of benfotiamine and/or vitamin B1-6-12 discontinued less than 7 days before study enrollment.
• Current use of vitamin B6 supplementation or medications containing vitamin B6 at a dose >100 mg/day.