Xingpi Yanger Granule combined with conventional medication for the treatment of nocturnal enuresis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE

This systematic review aims to determine the clinical efficacy and safety of Xingpi Yanger Granule (XPYEG) in combination with conventional medication for the treatment of Nocturnal Enuresis based on existing data.

METHODS

A systematic search was conducted across the China National Knowledge Infrastructure (CNKI), Wanfang Data, China Biomedical Literature Database (CBM), VIP, PubMed, Embase, Cochrane Library, and Web of Science databases to identify relevant RCTs on the auxiliary treatment of NE in children using XPYEG from the inception of each database up to August 2025. The risk of bias in the included RCTs was assessed using the Cochrane Risk of Bias tool (ROB2). Meta-analysis was performed using Review Manager, and the sensitivity analysis was conducted using Stata 18 software. The quality of evidence was evaluated with the GRADE approach. Furthermore, Trial Sequential Analysis (TSA) was employed to determine the required sample size and to verify the reliability of the findings. The review protocol was registered and published on PROSPERO (CRD420251156842).

RESULTS

This study included 12 RCTs involving 1,138 patients. Compared with conventional therapy alone, the combination of XPYEG significantly improves core symptoms, which is clinically significant. Core Symptom and Functional Outcomes: Compared with the control group, adjunctive XPYEG therapy resulted in a notable reduction in the frequency of NE [MD = 1.55, 95% CI (0.66, 2.43), P < 0.00001], a metric of direct relevance to quality of life. This symptomatic relief was supported by overall response rate [RR = 1.25, 95% CI (1.18, 1.32), P < 0.00001] and objective functional improvements, including a significant increase in age-expected bladder capacity [MD = 41.31, 95% CI (36.31, 46.32), P < 0.00001]. Long-term Trajectory and Safety: The combined regimen was further associated with a substantially lower risk of symptom recurrence [RR = 0.30, 95% CI (0.18, 0.49), P < 0.00001] and a reduced incidence of adverse reactions [RR = 0.35, 95% CI (0.15, 0.80), P < 0.00001], underscoring its potential as a sustainable and well-tolerated adjunctive strategy. Biochemical Correlates: Accompanying these clinical benefits, favorable modulations were observed in antidiuretic hormone (AVP) levels [MD = 6.40, 95% CI (5.18, 7.62), P < 0.00001], urinary osmolality [MD = 44.61, 95% CI (38.72, 50.48), P < 0.00001] and related second messenger pathways (cAMP, cGMP, and BVWI). While statistically significant, these findings serve primarily as supportive mechanistic rationale rather than direct indicators of patient-centered benefit.

CONCLUSION

Xingpi Yanger Granule may improve overall response, moderately reduce urinary frequency, and increase bladder capacity, while also lowering the recurrence rate and the incidence of adverse events. However, given that the evidence is limited in scope and rated as low to moderate quality, current conclusions should be interpreted with caution. Well-designed, large-scale, multicenter randomized controlled trials are needed to validate these potential benefits.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO CRD420251156842.