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.

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.

Copyright © 2026 Liu, Wang, Hu, Jia, Wu, Fu, Zheng and Sun.