The high occurrence and economic cost of diabetic peripheral neuropathy requires a more informed and precise approach to future therapy development. No approved disease modifying therapies currently exist, though exercise, dietary restriction, and bariatric surgery show some early favorable findings. Central to this concept is a realization that type 1 diabetes and type 2 diabetes mechanisms are intrinsically different: while peripheral neuropathy in type 1 diabetes is responsive to interventions aimed at controlling hyperglycemia (high blood sugar), peripheral neuropathy in type 2 diabetes requires interventions aimed at metabolic syndrome components (e.g. obesity, hypertension, and high fat levels in the blood). Through a greater appreciation of diabetic peripheral neuropathy mechanisms, particularly as it pertains to type 2 diabetes and metabolic syndrome, the potential for disease modifying therapies remains promising.