Efficacy and Safety of Diacerein in Patients With Inadequately Controlled Type 2 Diabetes: A Randomized Controlled Trial

OBJECTIVE To assess, in a randomized, double-blind, and placebo-controlled trial, the efficacy and safety of diacerein, an immunemodulator anti-inflammatory drug, in improving glycemic control of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Eighty-four patients with HbA(1c) between 7.5 and 9.5% (58-80 mmol/mol) were randomized to 48-week treatment with placebo (n = 41) or diacerein 100 mg/day (n = 43). The primary outcome was the difference in mean HbA(1c) changes during treatment. Secondary outcomes were other efficacy and safety measurements. A general linear regression with repeated measures, adjusted for age, sex, diabetes duration, and each baseline value, was used to estimate differences in mean changes. Both intention-to-treat (ITT) analysis and per-protocol analysis (excluding 10 patients who interrupted treatment) were performed. RESULTS Diacerein reduced HbA(1c) compared with placebo by 0.35%(3.8mmol/mol; P = 0.038) in the ITT analysis and by 0.41% (4.5 mmol/mol; P = 0.023) in the per-protocol analysis. The peak of effect occurred at the 24th week of treatment (-0.61% [6.7 mmol/mol; P = 0.014] and -0.78% [8.5 mmol/mol; P = 0.005], respectively), but it attenuated toward nonsignificant differences at the 48thweek. No significant effect of diacerein was observed in other efficacy and safety measures. Diarrhea occurred in 65% of patients receiving diacerein and caused treatment interruption in 16%. Seven patients in the diacerein group reduced insulin dosage, whereas 10 in the placebo group increased it; however, mild hypoglycemic events were equally observed. CONCLUSIONS Diacerein reduced mean HbA(1c) levels, with peak of effect at the 24th week of treatment. The drug was well tolerated and may be indicated as adjunct treatment in patients with type 2 diabetes, particularly in those with osteoarthritis.