Effect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: A randomized controlled trial

Diacerein seems to improve metabolic control and reduce inflammatory marker levels in individuals with type 2 diabetes mellitus (Type 2 DM), but for participants with chronic kidney disease (CKD) its effect is unknown. This study aimed to evaluate the effect of diacerein vs. placebo on urinary albumin/creatinine ratio (ACR), glomerular filtration rate (GFR), and inflammatory cytokines in type 2 DM participants with CKD. Blood pressure (BP) and metabolic control were secondary outcomes. This randomized, placebo-controlled, parallel trial of adjuvant treatment of type 2 DM with diacerein enrolled seventy-two participants with CKD, aged 30–80 years, with glycated hemoglobin levels from 53–97 mmol/mol (7.0–11.0%), receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antidiabetic agents. Participants randomized to diacerein or placebo were followed-up up to 90 days. Both groups had a marked reduction in ACR, but there was no effect on glomerular filtration rate. While the diacerein group had reduced TNF-α levels at the 75th percentile with a borderline significance (P = 0.05), there were no changes in the IL levels at the 75th percentile.Diacerein prevented the increase in blood glucose to the level observed in the placebo group (P = 0.04), improving metabolic control by 74%, reducing 24-hour diastolic BP, nighttime systolic and diastolic BP compared to the placebo group. In conclusion, among patients with type 2 DM and CKD, diacerein does not have an effect on ACR or GFR, but slows metabolic control deterioration and is associated with lower nighttime systolic and diastolic blood pressure.Trial registration: Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clinicos; ReBeC) U1111-1156-0255双醋瑞因（Diacerein）似乎可改善2型糖尿病（Type 2 DM）患者的代谢控制并降低炎症标志物水平，但针对慢性肾病（CKD）患者，其疗效尚不明晰。本研究旨在评估双醋瑞因对比安慰剂，对合并慢性肾病的2型糖尿病患者的尿白蛋白/肌酐比值（ACR）、肾小球滤过率（GFR）及炎症细胞因子的影响。血压（BP）与代谢控制为次要结局指标。本项针对双醋瑞因辅助治疗2型糖尿病的随机、安慰剂对照平行组试验，共纳入72名年龄30~80岁、糖化血红蛋白水平介于53~97 mmol/mol（7.0%~11.0%）、正在接受血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂及降糖药物治疗的合并慢性肾病的2型糖尿病患者。受试者被随机分配至双醋瑞因组或安慰剂组，随访时长最长达90天。两组患者的ACR均显著降低，但未观察到对肾小球滤过率的影响。双醋瑞因组在75分位处的肿瘤坏死因子-α（TNF-α）水平有所降低，呈临界显著性差异（P=0.05），但75分位处的白细胞介素（IL）水平未出现变化。双醋瑞因可阻止血糖升高至安慰剂组所观察到的水平（P=0.04），使代谢控制改善74%，相较于安慰剂组，可降低24小时舒张压、夜间收缩压及舒张压。综上，在合并慢性肾病的2型糖尿病患者中，双醋瑞因对ACR或GFR无显著影响，但可延缓代谢控制恶化，且与更低的夜间收缩压及舒张压相关。试验注册：巴西临床试验注册库（Registro Brasileiro de Ensaios Clinicos; ReBeC）U1111-1156-0255