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A prospective case-control study conducted in T2D patients with concurrent symptomatic peripheral neuropathy found that patients who had received metformin for more than 6 mo with a mean cumulative metformin exposure of 3389.5 g, compared with those without metformin exposure, had lower cobalamin levels and higher fasting MMA and homocysteine levels accompanied by more severe peripheral neuropathy (assessed by clinical and electrophysiological markers)[48]