Efficacy and safety of benfotiamine in diabetic peripheral neuropathy: a systematic review and meta-analysis
S. Lamlertpanya1, T. Suansanae2
1Thammasat University, Pharmacy, Bangkok, Thailand, 2Mahidol University, Pharmacy, Bangkok, Thailand
Background: Benfotiamine, a lipid-soluble vitamin B1 has attracted interest in the field of diabetic peripheral neuropathy (DPN) because of its target key pathogenic pathways by enhancing transketolase activity and diverting glycolytic intermediates away from harmful metabolic pathways. Consequently, benfotiamine has been proposed as a potential treatment for DPN. However, clinical trial evidences remain limited and heterogeneous.
Aims & Objectives: To evaluate the efficacy and safety of oral benfotiamine (150–600 mg) in DPN.
Method: PubMed and the Cochrane Library were searched for randomized controlled trials of benfotiamine in DPN from 1966 to 2026. Trials comparing oral benfotiamine with placebo or other active treatments were included. The primary outcome was pain intensity expressed as change from baseline with 95% confidence intervals (CIs). Secondary outcomes included neuropathy assessment score; which categorized as sensory-specific scores (e.g. total symptom score (TSS)) or composite scores (assessing motor, sensory and autonomic; e.g. neuropathy disability score (NDS)), nerve conduction study (NCS) parameters and adverse events (AEs). Outcomes not amenable to meta-analysis were synthesized narratively.
Results: Thirty studies were identified. There were only six randomized controlled trials met the inclusion criteria (n=422). Meta-analysis of pain intensity from three trials (total n=193; benfotiamine group n = 73) involving participants with low to moderate baseline pain intensity demonstrated a non-statistically significant trend toward reduction pain scores within-group of benfotiamine (-0.947 pain score; 95% CI −2.50 to 0.61). Pooled analysis between-group from two trials also showed a non-statistically significant trend toward reduction pain compared with placebo. Substantial heterogeneity was observed in the pooled pain analysis (I2=86-99%), indicating marked variability in effect estimates across studies.
For secondary outcomes, across studies, neuropathy assessment scores were heterogeneous precluding quantitative synthesis. Only NDS feasible for meta-analysis, pooled data from two trials showed non-statistically significant improvement trend (-0.23 NDS; 95% CI -0.87 to 0.40) with substantially heterogeneity observed.
From narrative synthesis, neuropathy outcome was inconsistent and generally showed small, non-significant changes. However, sensory-focused outcomes assessed by TSS showed trends toward improvement, particularly in pain and numbness.
Meta-analysis of NCS outcomes was not feasible because of limited data. Benfotiamine monotherapy showed no significant effect on nerve conduction parameters, whereas combination therapy with vitamin B6 and B12 demonstrated improvement in peroneal nerve conduction velocity; however, the clinical relevance of these findings remains uncertain. Across studies, safety profiles were consistent, with no significant differences in adverse events compared with placebo and no serious adverse events reported.
For secondary outcomes, across studies, neuropathy assessment scores were heterogeneous precluding quantitative synthesis. Only NDS feasible for meta-analysis, pooled data from two trials showed non-statistically significant improvement trend (-0.23 NDS; 95% CI -0.87 to 0.40) with substantially heterogeneity observed.
From narrative synthesis, neuropathy outcome was inconsistent and generally showed small, non-significant changes. However, sensory-focused outcomes assessed by TSS showed trends toward improvement, particularly in pain and numbness.
Meta-analysis of NCS outcomes was not feasible because of limited data. Benfotiamine monotherapy showed no significant effect on nerve conduction parameters, whereas combination therapy with vitamin B6 and B12 demonstrated improvement in peroneal nerve conduction velocity; however, the clinical relevance of these findings remains uncertain. Across studies, safety profiles were consistent, with no significant differences in adverse events compared with placebo and no serious adverse events reported.
Discussion & Conclusions: Current analyses suggests that benfotiamine is safe but does not statistically significant reduce pain and overall neuropathy symptom scores in DPN. However, the strength of the evidence is limited by the small number of included studies and substantial heterogeneity. While a potential benefit on sensory symptoms cannot be excluded, heterogeneity of outcome measures and limit sensitivity of commonly used symptom scales preclude definitive conclusions. Notably, a trend toward improvement in sensory neuropathy symptoms with a signal suggesting potential benefit for numbness was observed.
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