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The honest boundary is that even the coherent pairing is a mechanistic hypothesis with no human validation, so the most defensible research posture is to study the single compound at its documented dose first, and treat any combination as a further, clearly-labelled research question rather than a default

Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment

Treatment with lipoic acid methylcobalamin for 2-4 weeks is associated with better outcome in nerve conduction velocity and neuropathic symptoms

3 Vegans and vegetarians may also require B12 treatment, especially vegan women who are pregnant or breastfeeding