Efficacy and safety of methylcobalamin, alpha lipoic acid and pregabalin combination versus pregabalin monotherapy in improving pain and nerve conduction velocity in type 2 diabetes associated impaired peripheral neuropathic condition. [MAINTAIN]: Results of a pilot study

BACKGROUND AND OBJECTIVE: To assess whether methylcobalamin and alpha lipoic acid (ALA) added to pregabalin provide additional benefit compared to pregabalin alone in type 2 diabetes mellitus associated peripheral neuropathy. SETTING AND DESIGN: An open label, randomized, controlled parallel-group pilot study. MATERIALS AND METHODS: Thirty adult patients with type 2 diabetes mellitus with symptoms of peripheral neuropathy for ≥6 months were randomized to receive pregabalin 75 mg, methylcobalamin 750 μg, and ALA 100 mg (PMA, n = 15); or pregabalin 75 mg (PG, n = 15) for 12 weeks. Assessment variables were numeric rating scale (NRS), sleep interference scores (SIS), response rate to pain, and global assessment for the usefulness of therapy. The nerve conduction velocity was assessed for sensory and motor nerves. Safety assessment included adverse events reported by the patients, clinical laboratory, and general medical, neurological examinations. STATISTICAL ANALYSIS: Efficacy analyses were done on per-protocol (PP) population, whereas safety analyses were done on intent-to-treat (ITT) population. RESULTS: Significant improvement was seen in pain and sleep interference in both groups. Mean nerve conduction velocity of left common peroneal nerve (CPN) showed significant improvement in PMA group at week 12 compared to baseline (P = 0.018). For right CPN both groups showed significant improvement. (PMA, P = 0.002, PG, P = 0.007). For sensory testing, at week 12, right superficial peroneal nerve showed reduction in nerve conduction velocity in PG group compared to baseline (P = 0.043). CONCLUSION: Methylcobalamine, ALA and pregabalin combination provides pain relief and improves sleep interference. Addition of methylcobalamin and ALA to pregabalin improves the nerve function. Due to small sample size, most of the efficacy parameters could not reach significant difference between groups; hence benefit of the 3-drug-combimation should be interpreted with reservation.