Differential efficacy and anti-inflammatory mechanisms of Bailing Preparations versus Huangkui Capsules combined with SGLT-2 inhibitors for diabetic kidney disease: a network meta-analysis and GRADE assessment.

BACKGROUND: While sodium-glucose cotransporter 2 (SGLT-2) inhibitors serve as the cornerstone of therapy for diabetic kidney disease (DKD), a specific subset of patients continues to face residual risks, manifested as persistent proteinuria or declining renal function. Bailing Preparations and Huangkui Capsules are widely employed adjunctive Commercial Chinese polyherbal preparations (CCPPs). However, rigorous data differentiating their specific efficacy profiles-particularly regarding anti-inflammatory targets when paired with SGLT-2 inhibitors-remain undefined.

METHODS: Computerized searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Database, VIP Database, China Biomedical Literature Service System (Sinomed), and Bailing Preparation + SGLT-2i, Huangkui Capsule + SGLT-2i, and SGLT-2i monotherapy for the treatment of DKD. The search period covered from the establishment of each database to December 2025. The risk of bias was evaluated using the Cochrane RoB 2.0 tool, a network meta-analysis was performed using Stata 19.5, and the quality of evidence was assessed using the GRADE method.

RESULTS: The final analysis included 18 RCTs, involving a total of 1,564 participants. The results of the network meta-analysis showed: (1) Renal function and clinical efficacy: In terms of renal function protection, the Bailing preparation had the most significant effect in reducing serum creatinine (Scr) (MD = -12.31, 95% CI: -17.14, -7.48), and its Surface Under the Cumulative Ranking curve (SUCRA) probability ranking (81.8%) was the highest. The ranking results of the overall clinical efficacy (SUCRA = 79.1%) also supported this trend, with the Bailing preparation slightly superior to Huangkui Capsules. (2) Proteinuria and metabolism: Regarding proteinuria and metabolic indicators, Huangkui Capsules demonstrated unique advantages. In terms of 24-h urine protein quantification, Huangkui Capsules was the only intervention measure with a significant reduction effect (MD = -0.47, 95% CI: -0.77, -0.18). Additionally, its effects on fasting blood glucose (FPG) and 2-h post-meal blood glucose (2hPG) ranked the highest among all intervention measures (SUCRA values were all >90%). (3) Anti-inflammatory mechanism: The Bailing preparation specifically reduced systemic inflammatory markers (TNF-α and CRP), while Huangkui Capsules reduced local inflammatory mediators IL-6. (4) Safety: The SUCRA value of Huangkui Capsules was the highest (78.6%), indicating better safety.

CONCLUSION: Both Bailing Preparations and Huangkui Capsules can enhance the efficacy of SGLT-2i. Bailing Preparations focuses on protecting renal function by inhibiting systemic inflammation mediated by TNFα and CRP; Huangkui Capsules focuses on regulating glucose metabolism and inhibiting local damage mediated by IL-6 to reduce proteinuria.