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.