Abstract
INTRODUCTION: Shunting of glycolytic intermediates into the pentose phosphate pathway via transketolase activation by benfotiamine has been suggested to protect from hyperglycemia-induced microvascular damage, but the long-term effects of benfotiamine on diabetic sensorimotor polyneuropathy (DSPN) remain unclear. RESEARCH DESIGN AND METHODS: This 1:1 randomized double-blind, placebo-controlled parallel group monocentric phase II trial compared the efficacy and safety of 1-year treatment with benfotiamine 300 mg two times per day versus placebo over 12 months in participants with type 2 diabetes and mild-to-moderate symptomatic DSPN. The primary endpoint was the change in corneal nerve fiber length (CNFL) assessed by corneal confocal microscopy (CCM) from baseline to 12 months. Secondary endpoints included three other CCM parameters, skin biopsy (four parameters), nerve conduction studies (13 measures), quantitative sensory testing (six parameters), cardiovascular autonomic function tests (17 indices), sudomotor function tests (five parameters), 15 clinical scores and scales for neuropathic symptoms and signs and 13 health-related quality of life and depression instruments. Pharmacokinetics included measurement of six thiamine analytes in blood. RESULTS: A total of 57 participants underwent randomization. The changes from baseline to 12 months in CNFL did not differ between the two groups. The corresponding changes in the secondary morphometric, functional and clinical neuropathic outcomes as well as quality of life were also similar in the two groups. Only the Neuropathy Symptom Score tended to improve after benfotiamine treatment (p=0.098 vs placebo). Benfotiamine treatment increased the concentrations of all six thiamine analytes studied (p≤0.003 vs placebo). Safety analysis showed no relevant differences between the groups in the rates of adverse events. CONCLUSIONS: In type 2 diabetes individuals with mild-to-moderate symptomatic DSPN, treatment with benfotiamine for 12 months was well tolerated, but had no significant effects on multiple morphometric, neurophysiological and clinical measures of neuropathy. TRIAL REGISTRATION NUMBER: European Clinical Trials Database (EudraCT) 2017-003054-16 registered on April 10 (https://eudract.ema.europa.eu/), 2018 and German Register for Clinical Trials DRKS00014832 registered on August 3, 2018 (https://drks.de/search/de).