The Effect of Diacerein on Type 2 Diabetic Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis

Abstract

Aims. To figure out the effect of diacerein supplementation on type 2 diabetes mellitus (T2DM). Methods. An electronic search was processed on Pubmed, Embase, and Cochrane library for randomized controlled trials (RCTs) comparing the efficacy of diacerein with placebo on T2DM. The primary outcome was fasting blood glucose (FBG). Trial sequential analysis (TSA) was used to test the reliability of this pooled outcome. Secondary outcomes were glycosylated hemoglobin A1c (HbA1c), body mass index (BMI), lipid profiles, hematological indexes including hematocrit and platelet count, and systematic inflammatory level expressed as a C-reactive protein (CRP) level. Safety outcome was the rate of complications. The difference in continuous data was measured by mean difference (MD) and 95% confidence interval (CI), while the difference of dichotomous data was calculated by relative risk (RR) and 95% CI. A two-tailed P<0.05 was regarded as statistically significant. Results. Five RCTs with 278 participants were included. Compared with control, diacerein provided significant improvement on FBG (MD -0.52; 95% CI (-0.89~-0.14); P=0.007), but TSA showed that this positive effect required more support. Besides, diacerein also significantly improved HbA1c (MD -0.71; 95% CI (-1.07~-0.36); P<0.001), BMI (MD -0.40; 95% CI (-0.49~-0.31); P<0.001), and CRP level (MD -1.49; 95% CI (-2.78~-0.19); P=0.02). No superiority was noted in favor of either treatment regarding lipid profiles or hematological indexes. Among all complications, diacerein caused significantly more gastrointestinal syndromes (RR 1.39; 95% CI (1.08~1.77); P=0.009). Conclusion. Based on the current analysis, diacerein as an add-on treatment provided better glycemic control for T2DM but this benefit requires more verification. Compared with control, additional diacerein also lowered body weight and CRP level in T2DM, but increased the rate of gastrointestinal syndromes.

Protective Role of St. John’s Wort and Its Components Hyperforin and Hypericin against Diabetes through Inhibition of Inflammatory Signaling: Evidence from In Vitro and In Vivo Studies

“…Novel anti-inflammatory drugs included IL-1β receptor antagonists, such as canakinumab, initially considered capable of improving both insulin secretion and tissue insulin sensitivity, but later proved to have insufficient clinical efficacy in clinical trials [69]. Diacerein, another inhibitor of IL-1β used so far in osteoarthritis therapy, is currently being tested in Phase III trials for treatment of T2D (NCT02242149) [70]. Finally, anti-TNF-α compounds like etanercept, infliximab, and adalimumab were also shown to reduce insulin resistance in T2D [71].…”

Diacerein ameliorates kidney injury induced by cisplatin in rats by activation of Nrf2/Ho-1 pathway and Bax down-regulation

“…Diacerein inhibits the nitric oxide production that explains its anti-inflammatory and anti-osteoarthritis properties ( Abdelaziz et al, 2018 ). Rhein, an active metabolite of diacerein, has nephroprotective, antioxidant, anti-inflammatory, hepatoprotective, anticancer, chondroprotective, antimicrobial, antidiabetic activities ( Zhou et al, 2015 , Guo et al, 2020 , de Oliveira et al, 2020 ) so this study targets to clarify diacerein effect on the cisplatin-induced renal injury in rats.…”

Does Aerobic plus Machine-Assisted Resistance Training Improve Vascular Function in Type 2 Diabetes? A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis

“…Given sparse data and repeated significance testing, the risk of type I error might be elevated by cumulative meta-analyses [ 28 , 29 , 30 , 31 ]. To control this potential risk, trial sequential analysis (TSA) was launched (TSA software version 0.9 Beta; Copenhagen Trial Unit, Copenhagen, Denmark) for all measurements by empirical method for the estimation of the required information size.…”