Oral administration of the combination prescription product containing L-methylfolate, pyridoxal-5’-phosphate, and methylcobalamin (MPM) has shown to increase epidermal nerve fiber density in humans, reduce neuropathic pain and restore sensation in patients with diabetic neuropathy (DPN).  It is believed to increase vascular perfusion through lowering homocysteine and increasing nitric oxide levels. OBJECTIVES: Evaluate the clinical and economic impact of orally-administered MPM on patients with diabetic peripheral neuropathy (DPN) in a managed care setting. METHODS: Data were obtained from the 30+ million member HealthCore Integrated Research Databaseä. Patients with at least 1 claim for diabetes, antidiabetic agents and DPN and ≥2 claims for MPM between July 1, 2004 and April 30, 2007, with ≥6 months pre and ≥12 months post index eligibility were matched 2:1 on age, gender and health plan region with non-MPM treated patients. Cost comparisons were performed on the population <65 years old to assure full capture of health care costs. RESULTS: A total of 89 MPM treated patients and 178 matched controls were identified, 65% were male and mean (SD) age was 60.1 (±9.3) years. MPM treated patients were more likely to be treated with anticonvulsants in the pre-index period (p<0.01). There was a 31% reduction in the use of anticonvulsants post-index for the MPM group and a 10% reduction in the control group. There was a meaningful albeit non-significant cost difference in the 12 month post-index DPN related costs between the <65 year old MPM and control groups ($1029 n=56 vs. $1401 n=112). CONCLUSIONS: This observational cohort study demonstrated a reduction in the use of anticonvulsant medication among the MPM cohort, perhaps denoting a reduction in the need for pain medication, and costs related to DPN were lower in the MPM group.  Additional randomized controlled trials need to be conducted to validate these results.