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Blood-activating and collateral-unblocking traditional Chinese medicine formulas combined with mecobalamin for peripheral neuropathy in type 2 diabetes: a systematic review and Bayesian network meta-analysis

In brief

19 trials link Chinese formulas to better nerve scores, with very low certainty

Across 2,090 adults with type 2 diabetes and neuropathy, most traditional Chinese medicine formulas added to mecobalamin were associated with better symptom scores or nerve conduction than mecobalamin alone. Evidence was rated very low certainty, and safety reporting was inadequate; the formula rankings are exploratory, not a basis for choosing treatment.

Journal
Frontiers in endocrinology (Q1)
Published
16 September 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Zijian Liu, Yue Wang, An Hu, Shaowen Jia, Tingyu Wu, Yuchen Fu, et al.
PMID
42818718
DOI
10.3389/fendo.2026.1888494

Why clinicians should know about it

Abstract

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a leading cause of neuropathic pain, disability and lower-limb amputation, and the pharmacological options currently available do little to reverse established nerve injury. Compound traditional Chinese medicine preparations that activate blood circulation and unblock the collaterals have shown promise as add-on therapy to neurotrophic treatment, improving nerve conduction and relieving symptoms, but head-to-head comparisons between individual formulas are lacking. METHODS: PubMed, Embase, the Cochrane Library, CNKI, Wanfang and other databases were searched to July 2026 for randomised controlled trials comparing a blood-activating, collateral-unblocking formula plus mecobalamin with mecobalamin alone in adults with type 2 diabetes and peripheral neuropathy. The primary outcome was the Toronto Clinical Scoring System (TCSS); secondary outcomes were motor and sensory conduction velocity (MCV, SCV) of the median and common peroneal nerves, together with adverse events. Mean differences (MD) and 95% credible intervals were estimated in a Bayesian random-effects model, and ranking distributions were summarised as the surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed with RoB 2 and certainty of evidence with CINeMA (Confidence in Network Meta-Analysis). RESULTS: Nineteen randomised controlled trials (2,090 participants) were included. All were conducted in China, and most nodes were informed by a single trial. Relative to mecobalamin alone, most add-on regimens improved TCSS and nerve conduction velocity. Credible intervals excluded zero for 9 of 12 formulas for TCSS, 7 of 14 for median nerve MCV, 3 of 14 for median nerve SCV, 5 of 14 for peroneal nerve MCV and 8 of 9 for peroneal nerve SCV. By SUCRA, Yiqi Huashi Tongbi Formula ranked first for TCSS (90.3%; MD -3.49, 95% CrI -5.17 to -1.81), Shengyang Sanhuo Decoction for median nerve MCV (85.6%; MD 4.16, 95% CrI 1.58 to 6.78), Xiaoma Zhitong Capsule for median nerve SCV (84.4%; MD 4.19, 95% CrI 0.88 to 7.58), Modified Buyang Huanwu Decoction for peroneal nerve MCV (79.2%; MD 3.78, 95% CrI 0.83 to 6.72) and Jiangtang Tongluo Tablet for peroneal nerve SCV (95.2%; MD 4.08, 95% CrI 2.38 to 5.78). Eight of the 19 trials made no mention of adverse-event monitoring, and none reported numerical laboratory safety data. The available information is insufficient to evaluate the safety of these add-on regimens. CONCLUSION: Adding blood-activating, collateral-unblocking traditional Chinese medicine to mecobalamin was associated with improvement in TCSS and in nerve conduction velocity in patients with DPN. Certainty of evidence was very low for every comparison, however, and prediction intervals crossed the line of no effect for three outcomes, indicating that the direction of effect could change in a new study. The rankings are exploratory and hypothesis-generating: they are not a sufficient basis for inferring definite clinical efficacy or for choosing a formula for an individual patient, and they require confirmation in adequately powered, prospectively registered, blinded multicentre head-to-head trials. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025123604.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.