Efficacy and Safety of Tangshen Formula on Patients with Type 2 Diabetic Kidney Disease: A Multicenter Double-Blinded Randomized Placebo-Controlled Trial

Abstract

BackgroundPersons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD.MethodsThe study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events.FindingsAfter 24 weeks of treatment, no statistically significant difference in UAER (TSF −19.53 μg/min compared with placebo −7.01 μg/min, with a mean difference of −12.52 μg/min; 95%CI, −68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF−0.21 g compared with placebo 0.36 g, with a mean difference of −0.57g; 95%CI, −1.05 to −0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, −0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events.ConclusionsBased on conventional treatments, TSF appears to provide additional benefits compared with placebo in decreasing proteinuria and improving eGFR in DKD patients with macroalbuminuria. Nevertheless, further study is needed to evaluate TSF treating patients with microalbuminuria.Trial RegistrationChinese Clinical Trial Registry ChiCTR-TRC-10000843

Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis

“…Multiple clinical studies by Ping Li’s research group have demonstrated the efficacy of the Tangshen formula in attenuating diabetic kidney disease in rodent models and human patients [25]. Notably, a 2015 multicenter RCT in type 2 diabetic patients with diabetic kidney disease has also revealed that the Tangshen formula produces a significant decrease in 24-hour urinary protein as well as significant improvements in the estimated glomerular filtration rate (eGFR) relative to placebo [26]. In addition, our finding regarding the efficacy of ramipril ACEI monotherapy in type 2 diabetes patients with microalbuminuria concords with a previous network meta-analysis by Vejakama et al, which demonstrated a superior reno-protective effect with ACEI monotherapy or ARB monotherapy over CCB monotherapy or placebo in type 2 diabetic patients [27].…”

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice

“…The db/m mice were used as controls (n=9, db/m). The TSF dosage was based on our previous study and standard conversion formula (body surface areas) (15,16). Body weight was measured weekly (g).…”

Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective

“…In short, counting on the undiagnosed patients who do not yet realize their condition, the overall prevalence of DN is unoptimistic. Particularly, Table 1 summarizes selected studies that evaluated DN incidences and outcomes in diabetic nephropathy patients and also are related to the topic [10–16]. American Diabetes Association accurately defined diabetes mellitus as “a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both” [17].…”

“…Historically, conventional medicines, such as ACEI or ARB, are not able to totally prevent the development of DN [16]. Thus, there is an urgent need to find new effective agents to delay the progression of DN.…”