Efficacy and safety of Buyang Huanwu Decoction combined with α-lipoic acid for diabetic peripheral neuropathy: a systematic review with in-depth heterogeneity deconstruction and methodological appraisal.

BACKGROUND

Diabetic peripheral neuropathy (DPN) is a common diabetes complication. Buyang Huanwu Decoction (BYHWD) combined with α-lipoic acid (ALA) is used clinically, but evidence consistency and heterogeneity sources remain unexplored.

OBJECTIVE

To evaluate efficacy/safety of BYHWD+ALA for DPN and deconstruct heterogeneity via a multi-tiered framework.

METHODS

We searched PubMed, Web of Science, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and CBM up to December 2025 for RCTs. Two reviewers independently screened studies, extracted data, and assessed risk of bias (Cochrane tool). Meta-analysis used RR (dichotomous) and SMD (continuous) with 95% CI. Heterogeneity (I²) was explored through subgroup analysis, sensitivity analysis, meta-regression, and descriptive synthesis.

RESULTS

Twelve RCTs (926 patients) were included. BYHWD+ALA significantly improved overall response rate (RR = 1.24, 95%CI 1.17-1.32; I²=0%) and TCM syndrome scores (SMD=-0.76, 95%CI -0.98 to -0.54). For nerve conduction velocity (NCV), fundamental heterogeneity emerged (I²>92%). A five-tiered analysis revealed that only peroneal nerve motor NCV showed a robust improvement trend (SMD = 1.01, 95%CI 0.48-1.54), though heterogeneity remained high (I²=92%). Heterogeneity sources included non-standardized NCV measurement and complex intervention-patient matching. Oxidative stress markers (SOD, MDA, T-AOC) trended favorably; HbA1c and adverse events did not differ between groups.

CONCLUSION

BYHWD+ALA safely improves subjective DPN symptoms, but NCV evidence is too heterogeneous to draw reliable quantitative conclusions. This study provides a methodological framework for deconstructing heterogeneity and guides future standardized research.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=1267606, identifier CRD420251267606.