Li H, Ren FH, Yang LP, Mao HM, Ma F, Wang YY, Jin Q, Liang PY, Zhan YL. Efficacy and safety of Bailing capsules combined with sodium glucose cotransporter inhibitors in diabetic kidney disease treatment. World J Diabetes 2026; 17(6): 120131 [DOI: 10.4239/wjd.120131]
Corresponding Author of This Article
Yong-Li Zhan, Professor, Department of Nephrology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 North Line Pavilion, Xicheng District, Beijing 100053, China. zhanyongli88@sina.com
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Li H, Ren FH, Yang LP, Mao HM, Ma F, Wang YY, Jin Q, Liang PY, Zhan YL. Efficacy and safety of Bailing capsules combined with sodium glucose cotransporter inhibitors in diabetic kidney disease treatment. World J Diabetes 2026; 17(6): 120131 [DOI: 10.4239/wjd.120131]
Han Li, Fei-Hong Ren, Li-Ping Yang, Hui-Min Mao, Fang Ma, Yu-Yang Wang, Qi Jin, Yong-Li Zhan, Department of Nephrology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Peng-Yuan Liang, Department of Nephrology, Yangquan Coal Industry Group Co., Ltd. General Hospital, Yangquan 045000, Shanxi Province, China
Co-corresponding authors: Peng-Yuan Liang and Yong-Li Zhan.
Author contributions: Li H was responsible for conceptualization, data curation, formal analysis, investigation, methodology, software, validation, visualization, writing - original draft, and writing - review & editing; Ren FH was responsible for conceptualization, formal analysis, investigation, methodology, software, validation, visualization, writing - original draft, and writing - review & editing; Yang LP was responsible for conceptualization, data curation, formal analysis, methodology, and writing - review & editing; Mao HM was responsible for funding acquisition, investigation, supervision, and writing - review & editing; Ma F was responsible for investigation, methodology, and writing - review & editing; Wang YY was responsible for investigation and writing - review & editing; Jin Q was responsible for methodology and writing - review & editing; Liang PY was responsible for conceptualization, data curation, formal analysis, methodology, project administration, writing - original draft, and writing - review & editing; Zhan YL was responsible for conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, writing - original draft, and writing - review & editing; Li H and Ren FH have contributed equally to this work and share first authorship, Liang PY and Zhan YL contributed equally and share corresponding authorship, all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82305210 and No. 82374419; and Major Research Project Funding Project of Science and Technology Innovation Project of China Academy of Chinese Medical Sciences, No. CI2021A01210.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Yong-Li Zhan, Professor, Department of Nephrology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 North Line Pavilion, Xicheng District, Beijing 100053, China. zhanyongli88@sina.com
Received: February 24, 2026 Revised: March 18, 2026 Accepted: April 23, 2026 Published online: June 15, 2026 Processing time: 116 Days and 2.1 Hours
Abstract
BACKGROUND
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Integrative approaches combining traditional Chinese medicine and Western pharmacotherapy have shown potential benefits.
AIM
To evaluate the efficacy and safety of Bailing capsules (BCs) combined with SGLT2is in DKD treatment.
METHODS
Randomized controlled trials (RCTs) were retrieved from China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Web of Science, EMBASE, and Cochrane Library up to September 14, 2025. Data extraction and quality assessment were performed independently by two reviewers using the Cochrane risk of bias tool. Meta-analysis was conducted with Stata 18.0, and trial sequential analysis (TSA) was applied to assess the robustness of evidence.
RESULTS
Fourteen RCTs involving 1919 patients were included. Compared with SGLT2is alone, BC plus SGLT2is significantly improved clinical efficacy [relative risk (RR) = 1.157, 95%CI: 1.102-1.216]; reduced fasting blood glucose [weighted mean difference (WMD) = -0.729, 95%CI: -0.976 to -0.482] and glycated hemoglobin (WMD = -0.680, 95%CI: -0.768 to -0.592) levels; altered renal function markers, including serum creatinine [SCr; standardized mean difference (SMD) = -1.033, 95%CI: -1.258 to -0.808], blood urea nitrogen (WMD = -1.158, 95%CI: -1.537 to -0.779), and β2-microglobulin (WMD = -1.237, 95%CI: -1.471 to -1.002) levels; and reduced 24-hour urinary protein levels (SMD = -1.329, 95%CI: -1.801 to -0.857). No significant increase in the incidence of adverse events was observed (RR = 0.939, P = 0.767). Subgroup analysis suggested that the optimal BC dosage was 1.0-3.0 g three times daily. TSA confirmed the reliability of the evidence for a reduction in SCr.
CONCLUSION
BC combined with SGLT2is appears to be effective and safe for improving glycemic control and renal function in DKD patients. Further high-quality, multicenter RCTs are warranted to validate these findings.
Core Tip: This meta-analysis of 14 randomized controlled trials including 1919 patients revealed that Bailing capsules combined with sodium-glucose cotransporter 2 inhibitors improved clinical efficacy, reduced blood glucose levels, and decreased serum creatinine levels and 24-hour urinary protein levels in patients with diabetic kidney disease (DKD). The safety profile of the combination therapy is comparable to that of control treatments and may provide a practical option for the integrated management of DKD.
Citation: Li H, Ren FH, Yang LP, Mao HM, Ma F, Wang YY, Jin Q, Liang PY, Zhan YL. Efficacy and safety of Bailing capsules combined with sodium glucose cotransporter inhibitors in diabetic kidney disease treatment. World J Diabetes 2026; 17(6): 120131
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and occurs in approximately 20%-40% of diabetic patients[1]. DKD is the main cause of end-stage kidney disease (ESKD)[2]. Currently, the comprehensive management of DKD relies on combined targeted therapy involving blood glucose, blood pressure, proteinuria, blood lipids and uric acid, as well as lifestyle intervention[3]. Among them, sodium-glucose cotransporter 2 inhibitors (SGLT2is) are recommended for DKD patients whose estimated glomerular filtration rate (eGFR) is ≥ 20 mL/minute/1.73m2 because of their cardiorenal protective effect. Additionally, SGLT2is can be prescribed to patients with decreased eGFRs[4]. However, although the EMPEROR-Reduced trial demonstrated a 25% reduction in cardiovascular death or heart failure hospitalization rates as the primary outcome in the empagliflozin treatment group, the residual risk still exceeded 15%[5]. Additionally, these drugs increase the risk of reproductive tract infections by promoting the excretion of large amounts of glucose through the urine, which may also be a potential factor promoting the further development of chronic kidney disease[6].
In recent years, increasing evidence has confirmed the important role of integrated traditional Chinese and Western medicine in the treatment of DKD[7]. The Bailing capsule (BC) tonifies the lungs and kidneys, providing benefits for essence and qi. This capsule is recommended for patients with DKD stage A2 to reduce the risk of progression to ESKD and improve renal function[8,9]. However, at present, no systematic reviews or meta-analyses have comprehensively evaluated the efficacy and safety of BCs combined with SGLT2is in the treatment of DKD. Therefore, this meta-analysis included randomized controlled trials (RCTs) that investigated the combination of BCs with SGLT2is for the treatment of DKD. The aim of this meta-analysis was to provide empirical guidance for the clinical application of this combination treatment.
MATERIALS AND METHODS
Search strategy
The China National Knowledge Infrastructure (https://www.cnki.net), Wanfang (https://www.wanfangdata.com.cn), VIP (http://www.cqvip.com), PubMed (https://pubmed.ncbi.nlm.nih.gov), Web of Science (https://www.webofscience.com), EMBASE (https://www.embase.com), and Cochrane Library (https://www.cochranelibrary.com) databases were searched from inception to September 14, 2025, to identify studies. A combination of subject and free words was used for retrieval and adjusted according to the retrieval system. The search terms used were as follows: Diabetic Nephropathies, Diabetic Nephropathy, Diabetic kidney disease, Bailing Capsule, Bailing Capsules. The search formulation was as follows: (Diabetic Nephropathies) OR (Diabetic Nephropathy) OR (Diabetic Kidney Disease); (Bailing Capsule) OR (Bailing Capsules); (Diabetic Nephropathies) OR (Diabetic Nephropathy) OR (Diabetic Kidney Disease) AND (Bailing Capsule) OR (Bailing Capsules).
Inclusion criteria
The inclusion criteria were as follows: (1) A type of study, namely, an RCT; (2) A type of participant, namely, patients with DKD according to the “Consensus on Clinical Management of Diabetes Mellitus Complicated with Chronic Kidney Disease in China”[3]; (3) A type of intervention, namely, experimental interventions that included SGLT2is alone or combined with BCs on the basis of basic treatment; and (4) A type of outcome indicator, namely, clinical effective rate, blood glucose [fasting blood glucose and glycated hemoglobin (HbA1c) levels], renal function [serum creatinine (SCr), blood urea nitrogen (BUN), and beta-2 microglobulin (β2-MG) levels], 24-hour urine protein (24h-UP) quantification, and the incidence of adverse reactions.
Exclusion criteria
The exclusion criteria were as follows: (1) Reviews or systematic evaluation studies, case reports, and experience summaries; (2) Basic experiments on animals or cells; (3) The use of other treatment methods that may affect the outcome judgment in addition to basic treatment; (4) Studies with insufficient details; or (5) Duplicate reports from the same study.
Study selection, data extraction and quality evaluation
Two researchers independently screened the studies and extracted the data according to the inclusion and exclusion criteria. Disagreements were resolved by consulting a third party. The following data were extracted: Author and year, sample size, age, baseline level, intervention measures, course of treatment, outcome indicators, and adverse reactions. The Cochrane risk of bias tool was used to assess the quality of the included studies across multiple domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases. The risk of bias graph was constructed using Review Manager (RevMan) 5.4.
Statistical analysis
Meta-analysis was performed using Stata 18.0, and trial sequential analysis (TSA) was performed using TSA 0.9.5.10. The relative risk (RR) and its 95%CI were used for dichotomous outcomes, and the weighted mean difference (WMD) or standardized mean difference (SMD) and 95%CI were calculated for continuous outcomes. The heterogeneity test included the χ2 test and I2 evaluation. A fixed effects model was used if P ≥ 0.1 and I2 ≤ 50%; otherwise, a random effects model was used, and sensitivity analyses were performed to further evaluate the sources of heterogeneity. For outcome indicators that included more than 10 studies, the risk of publication bias was evaluated through Egger’s test and funnel plots, and TSA was conducted.
RESULTS
Search results
A total of 1079 articles were identified. Through a stepwise screening process, 14 RCTs were ultimately included for analysis[10-23]. The study selection procedure is detailed in Figure 1.
Figure 1 Flow chart of study screening.
CNKI: Chinese National Knowledge Infrastructure; RCTs: Randomized controlled trials.
Study characteristics
All the included studies were Chinese studies involving 1919 patients, among which 965 were in the treatment group and 954 were in the control group. The basic characteristics of each study are shown in Table 1.
Table 1 Main characteristics of the 14 included trials.
Figure 2 Assessment of the risk of bias.
A: Risk of bias graph of the included studies; B: Risk of bias summary of the included studies.
Evaluation of efficacy and safety
A total of 9 studies reported the clinical effectiveness rate[11-13,16,17,19-21,23]. The forest plot revealed that there was no heterogeneity among the results (I2 = 0.0%, P = 0.619); therefore, the fixed effects model was used for analysis. The results indicated that compared with the control treatment, the combination of BCs and SGLT2is improved clinical efficacy (RR = 1.157, 95%CI: 1.026-1.216, P < 0.001; Figure 3A).
Figure 3 Forest plot of the clinical effective rate and incidence of adverse reactions.
A: Clinical effective rate; B: Incidence of adverse reactions. RR: Relative risk.
Blood glucose
Fasting blood glucose level: A total of 9 studies reported changes in fasting blood glucose levels[11,15-20,22,23]. Owing to the high degree of heterogeneity (I2 = 99.0%, P < 0.001), a sensitivity analysis was performed, as illustrated in Figure 4A. After one study[15] was excluded, heterogeneity persisted (I2 = 86.5%, P < 0.001), and a random effects model was subsequently applied. The results indicated that the effect of BCs combined with SGLT2is on reducing fasting blood glucose was greater than that of the control treatment (WMD = -0.729, 95%CI: -0.976 to -0.482, P < 0.001; Figure 4B). Subgroup analysis indicated that the combination therapy significantly decreased fasting blood glucose levels across all the tested dosage regimens: 1.0 g three times daily (WMD = -1.274, 95%CI: -2.537 to -0.012; P = 0.048); 1.5 g three times daily (WMD = -0.770, 95%CI: -0.930 to -0.610, P < 0.001); 2.0 g three times daily (WMD = -0.423, 95%CI: -0.599 to -0.246, P < 0.001); and 1.0-3.0 g three times daily (WMD = -1.080, 95%CI: -1.464 to -0.696, P < 0.001). The most pronounced therapeutic effect was observed at a dosage of 1.0 g three times daily, as presented in Figure 4C.
Figure 4 Meta-analysis of the glycemic effects of Bailing capsules combined with SGLT2is or SGLT2is alone.
A: Sensitivity analysis of fasting blood glucose levels; B: Forest plot of fasting blood glucose levels; C: Subgroup analysis of fasting blood glucose levels across different Bailing capsule dosages; D: Sensitivity analysis of glycated hemoglobin (HbA1c) levels; E: Forest plot of HbA1c levels. WMD: Weighted mean difference.
HbA1c levels: A total of 6 studies reported changes in HbA1c levels[11,16,17,19,22,23]. Owing to the high degree of heterogeneity (I2 = 94.7%, P < 0.001), a sensitivity analysis was performed, as illustrated in Figure 4D. Upon exclusion of one study[22], the high degree of heterogeneity was effectively eliminated (I2 = 40.2%, P = 0.154). Consequently, a fixed effects model was employed, revealing that compared with the control treatment, the combination therapy with BCs led to a significantly greater reduction in HbA1c levels (WMD = -0.680, 95%CI: -0.768 to -0.592, P < 0.001), as shown in Figure 4E. Owing to the limited number of studies included, a subgroup analysis based on different dosages of BCs was not performed.
Renal function
To ensure a comprehensive assessment of renal function in patients with DKD, three core biochemical markers were selected. SCr is a well-established indicator of glomerular filtration capacity. BUN reflects nitrogen metabolism and overall renal clearance, thereby complementing SCr in evaluating kidney performance. The β2-MG is a sensitive marker of tubular injury, providing additional information on renal tubular integrity. Taken together, these parameters offer a multidimensional evaluation of renal function and strengthen the reliability of comparative analyses.
SCr levels: A total of 12 studies reported changes in the SCr level[10-18,21-23]. Owing to the high degree of heterogeneity (I2 = 71.0%, P < 0.001), a sensitivity analysis was performed, as illustrated in Figure 5A. No significant outliers were identified, and a random effects model was subsequently applied. The results indicated that the effect of BCs combined with SGLT2is on reducing SCr was greater than that of the control treatment (SMD = -1.033, 95%CI: -1.258 to -0.808, P < 0.001; Figure 5B). Subgroup analysis indicated that the combination therapy significantly decreased the SCr concentration across all the tested dosage regimens: 1.0 g three times daily (SMD = -1.111, 95%CI: -1.576 to -0.645, P < 0.001), 1.5 g three times daily (SMD = -0.778, 95%CI: -0.924 to -0.633, P < 0.001), 2.0 g three times daily (SMD = -1.188, 95%CI: -1.671 to -0.705,P < 0.001), and 1.0-3.0 g three times daily (SMD = -0.783, 95%CI: -1.096 to -0.469, P < 0.001). Notably, heterogeneity was eliminated specifically within the 1.0-3.0 g three times daily subgroup, with the most pronounced therapeutic effect observed at the dosage of 2.0 g three times daily, as illustrated in Figure 5C.
Figure 5 Meta-analysis of the effects of Bailing capsules combined with SGLT2is or SGLT2is alone on renal function.
A: Sensitivity analysis of serum creatinine (SCr) levels; B: Forest plot of SCr levels; C: Subgroup analysis of SCr levels across different BC dosages; D: Sensitivity analysis of blood urea nitrogen (BUN) levels; E: Forest plot of BUN levels; F: Subgroup analysis of BUN levels across different BC dosages; G: Sensitivity analysis of beta-2 microglobulin (β2-MG) levels; H: Forest plot of β2-MG levels. WMD: Weighted mean difference; SMD: Standardized mean difference.
BUN levels: A total of 8 studies reported changes in BUN levels[11-13,17,20-23]. Owing to the high degree of heterogeneity (I2 = 93.6%, P < 0.001), a sensitivity analysis was performed, as illustrated in Figure 5D. No significant outliers were identified, and a random effects model was subsequently applied. The results indicated that the effect of BCs combined with SGLT2is on reducing BUN was greater than that of the control treatment (WMD = -1.158, 95%CI: -1.537 to -0.779, P < 0.001; Figure 5E). Subgroup analysis indicated that the combination therapy significantly decreased BUN levels across all the tested dosage regimens: 1.0 g three times daily (WMD = -1.452, 95%CI: -2.027 to -0.877, P < 0.001), 1.5 g three times daily (WMD = -0.340, 95%CI: -0.489 to -0.191, P < 0.001), 2.0 g three times daily (WMD = -0.835, 95%CI: -1.294 to -0.375, P < 0.001), and 1.0-3.0 g three times daily (WMD = -1.848, 95%CI: -3.455 to -0.241, P = 0.024). The most pronounced therapeutic effect was observed at dosages of 1.0-3.0 g three times daily, as presented in Figure 5F.
β2-MG levels: A total of 3 studies reported changes in β2-MG levels[14,15,19]. Owing to the high degree of heterogeneity (I2 = 96.2%, P < 0.001), a sensitivity analysis was performed, as illustrated in Figure 5G. Upon exclusion of one study[19], the high degree of heterogeneity was effectively eliminated (I2 = 0.0%, P = 0.807). Consequently, a fixed effects model was employed, revealing that compared with the control treatment, the combination therapy with BCs led to a significantly greater reduction in β2-MG levels (WMD = -1.237, 95%CI: -1.471 to -1.002, P < 0.001), as shown in Figure 5H. Owing to the limited number of studies included, a subgroup analysis based on different dosages of BC was not performed.
24h-UP
A total of 8 studies reported changes in 24h-UP[10,11,13,16,17,20,22,23]. Owing to the high degree of heterogeneity (I2 = 89.0%, P < 0.001), a sensitivity analysis was performed, as illustrated in Figure 6A. No significant outliers were identified, and a random effects model was subsequently applied. The results indicated that the effect of BCs combined with SGLT2is on reducing 24h-UP was greater than that of the control treatment (SMD = -1.329, 95%CI: -1.801 to -0.857, P < 0.001; Figure 6B). Subgroup analysis revealed differential effects on 24h-UP reduction across various dosage regimens of BCs in combination therapy: 1.0 g three times daily (SMD = -1.049, 95%CI: -2.022 to -0.076, P = 0.035); 1.5 g three times daily (SMD = -1.500, 95%CI: -1.670 to -1.330, P < 0.001); 2.0 g three times daily (SMD = -1.184, 95%CI: -2.444 to 0.075, P = 0.065); and 1.0-3.0 g three times daily (SMD = -1.797, 95%CI: -2.190 to -1.405, P < 0.001). The dosage of 1.0-3.0 g three times daily was associated with the elimination of heterogeneity and demonstrated the most pronounced therapeutic effect. In contrast, the 2.0 g three times daily regimen did not further increase the therapeutic effects of the combination therapy. These results are presented in Figure 6C.
Figure 6 Meta-analysis of the effects of Bailing capsules combined with SGLT2is or SGLT2is alone on 24-hour urine protein.
A: Sensitivity analysis of 24-hour urine protein (24h-UP); B: Forest plot of 24h-UP; C: Subgroup analysis of 24h-UP across different Bailing capsule dosages. SMD: Standardized mean difference.
The incidence of adverse reactions
A total of 9 studies reported changes in the incidence of adverse reactions[10,14-18,20-22]. The forest plot revealed that there was no heterogeneity among the results (I2 = 0.0%, P = 0.971); therefore, the fixed effects model was used for analysis. The results indicated that there was no significant difference in the incidence of adverse reactions between the two groups (RR = 0.939, 95%CI: 0.617-1.427, P = 0.767; Figure 3B).
Assessment of publication bias
Since the SCr level was the only outcome that was assessed in more than 10 studies, Egger's test was conducted on the SCr data, and funnel plots were constructed to evaluate whether there was publication bias. Egger's test revealed that P = 0.079. The funnel plot was essentially symmetrical (Figure 7). Therefore, there was no significant bias with respect to this outcome.
Figure 7 Funnel plot for the assessment of publication bias risk.
SMD: Standardized mean difference.
TSA
The TSA parameter settings were α = 0.05 and β = 0.2. The sample size was predicted. Additionally, sequential analysis was conducted on the SCr data. The TSA results revealed that the cumulative Z value (Z-curve, blue) crossed the TSA boundary value (curve A, red) and the traditional boundary value (dotted line B, green) after the inclusion of the first study[14], indicating that a positive conclusion was reached. After the inclusion of three studies[10,14,18], the sample size exceeded the expected amount of information by 230, suggesting that the combination of BCs with SGLT2is is effective in terms of reducing the SCr level in DKD patients (Figure 8).
This is the first study to systematically evaluate the efficacy and safety of BCs combined with SGLT2is for the treatment of DKD. The results revealed that the combination therapy effectively reduced the blood glucose levels of DKD patients (Figure 4), improved renal function (Figure 5), alleviated proteinuria (Figure 6), and improved clinical efficacy (Figure 3A). Moreover, there was no significant difference in the incidence of adverse reactions between the two groups (Figure 3B). These findings indicated that the therapy was effective and relatively safe. Subgroup analysis indicated that a dosage of 1.0-3.0 g administered three times daily contributed to a reduction in heterogeneity and was associated with enhanced therapeutic efficacy. These findings suggest that the clinical application of BC should be individualized to optimize its treatment outcomes. Moreover, Egger’s test revealed that P > 0.05, and the funnel plot was essentially symmetrical (Figure 7), indicating that there was no significant bias in this study. The TSA results further demonstrated that the evidence regarding the efficacy of BCs combined with SGLT2is in the treatment of DKD was reliable (Figure 8).
Traditionally, DKD has been considered a microvascular disease closely associated with glomerular hyperfiltration and dysfunction of glomerular podocytes[24,25]. In our study, we observed that compared with the control treatment, the combination therapy resulted in significantly greater reductions in SCr and BUN levels. These findings indicate that the combined regimen has superior effects on glomerular filtration and nitrogen metabolism in patients with DKD. SGLT2is can not only lower blood glucose levels by reducing the reabsorption of glucose in the proximal tubule but also restore glomerular hemodynamics by modulating adenosine metabolism to increase afferent arteriolar contraction and reduce efferent arteriolar contraction[26]. Therefore, the ability of SGLT2is to activate tubuloglomerular feedback and reduce hyperfiltration-mediated renal injury is considered a core mechanism of renal protection[27,28]. Moreover, recent studies have indicated that SGLT2is can ameliorate podocyte injury in DKD by rebalancing mitochondria-associated endoplasmic reticulum membranes[29]. Similar podocyte-protective effects have also been demonstrated in other types of kidney injury, such as lupus nephritis[30] and Alport syndrome[31]. Additionally, inflammation and fibrosis are considered key mediators of the development and progression of DKD[32]. The BC, a traditional Chinese medicinal preparation of Cordyceps, contains a variety of active ingredients, including D-mannitol, cordycepin, nine amino acids, multiple vitamins, carrier alkaloids, and trace elements. BCs can act on the process of blood glucose reduction through multiple pathways, including stimulating insulin secretion[33], increasing insulin resistance[34,35], enhancing insulin sensitivity[36], or regulating the transport and utilization of glucose[37]. Under nephropathy conditions, Cordyceps extract can alleviate renal injury by regulating autophagy, thereby inhibiting apoptosis and increasing the expression of organic anion transporters in the kidney[38]. Moreover, Cordyceps and its active components can also alleviate renal fibrosis by inhibiting the production of transforming growth factor-β1 and exerting anti-inflammatory effects to suppress epithelial-mesenchymal transition and reduce extracellular matrix accumulation[39].
In recent years, increasing evidence has shown that tubular cell injury and dysfunction also play crucial roles in the development and progression of DKD[40,41]. Therefore, tubular cells may be potential therapeutic targets for the treatment of DKD. SGLT2 is expressed primarily in the epithelial cells of the renal proximal tubule and is responsible for the majority of glucose reabsorption in the kidney[42]. In the diabetic environment, because of abnormal metabolism and hemodynamics in the body, the development and progression of DKD are accelerated[43]. Given the physiological characteristics of SGLT2 in the kidneys, SGLT2is can alleviate DKD-associated tubular injury through various mechanisms, such as by regulating renal energy metabolism through the inhibition of mTORC1 signaling in the tubules[44,45] and promoting arteriosclerosis to modulate hemodynamics[46]. This has made SGLT2is a current research hotspot. On the other hand, modern pharmacological studies have demonstrated that cordycepin, an active ingredient in the BC, can protect renal tubular epithelial cells by inhibiting inflammatory responses and apoptosis[47,48]. Recent evidence further substantiates the tubular protective role of Cordyceps, showing that it promotes the proliferation of proximal tubular cells while inhibiting their apoptosis. These actions contribute to the attenuation of oxidative stress and inflammatory injury and are likely mediated through the activation of the AKT and ERK signaling pathways[49]. Consequently, this study focused on the tubular protective effects of BC and its potential synergistic actions with SGLT2is in renal tubules, with the aim of providing new perspectives and strategies for the management of DKD. Nevertheless, although BCs and SGLT2is may exert favorable synergistic protective effects on renal tubules, only three studies have employed β2-MG, a sensitive marker of tubular injury, as an outcome indicator. This limitation reduces the strength of the available evidence and constrains the robustness of the conclusions that can be drawn from the present analysis.
In translating these findings into realworld clinical practice, importantly, the optimal dosing range identified in this metaanalysis (1.0-3.0 g administered three times daily) should not be interpreted as a uniform regimen for all patients. Although this dosage demonstrated the most favorable therapeutic response across the included trials, individualized adjustment remains essential in clinical settings. Factors such as patient age, baseline renal function, comorbid conditions, concomitant medications, and overall treatment tolerance may influence the appropriate dosing strategy. This patient-centered approach is consistent with the principles of integrative medicine, which emphasize tailoring therapy to individual physiological characteristics. Therefore, while the summarized dosing range provides a useful reference for clinical decision-making, personalized titration is necessary to ensure both safety and therapeutic effectiveness in diverse patient populations.
This study has several limitations that should be acknowledged. First, although the combination of traditional Chinese medicine and Western medicine is widely applied in China, the number of eligible trials was limited because SGLT2is have only recently become a research focus, and only published literature is available. Second, none of the included studies reported allocation concealment or blinding procedures, which may lower overall methodological quality and introduce potential bias, particularly for outcomes that rely on subjective assessment, such as clinical efficacy. Third, follow-up durations were generally short, and key endpoint indicators, including mortality and progression to ESKD, were not observed. These factors restrict the ability to evaluate long-term benefits and overall effectiveness. Despite these limitations, the present meta-analysis provides valuable preliminary evidence supporting the integrative use of BCs with SGLT2is and highlights the need for future high-quality, multicenter RCTs with extended follow-up to confirm and expand upon these findings.
CONCLUSION
The current evidence indicates that the combination of BCs and SGLT2is for the treatment of DKD is effective and relatively safe. However, the included RCTs did not focus on tubular function, which may be a direction for future research. Additionally, the limited number and quality of the included studies affected the strength of the argumentation of the results. More large-scale, multicenter RCTs with enhanced quality control are still needed to provide more effective evidence for clinical practice.
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P-Reviewer: Cai L, MD, PhD, Professor, United States; Wang KY, MD, Assistant Professor, China; Yuan Z, PhD, Assistant Professor, China S-Editor: Lin C L-Editor: A P-Editor: Yang YQ
