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

Abstract

To assess, in a randomized, double-blind, and placebo-controlled trial, the efficacy and safety of diacerein, an immune modulator anti-inflammatory drug, in improving glycemic control of patients with type 2 diabetes. Eighty-four patients with HbA_1c between 7.5 and 9.5% (58-80 mmol/mol) were randomized to 48-week treatment with placebo (<i>n</i> = 41) or diacerein 100 mg/day (<i>n</i> = 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. Diacerein reduced HbA_1c compared with placebo by 0.35% (3.8 mmol/mol; <i>P</i> = 0.038) in the ITT analysis and by 0.41% (4.5 mmol/mol; <i>P</i> = 0.023) in the per-protocol analysis. The peak of effect occurred at the 24th week of treatment (-0.61% [6.7 mmol/mol; <i>P</i> = 0.014] and -0.78% [8.5 mmol/mol; <i>P</i> = 0.005], respectively), but it attenuated toward nonsignificant differences at the 48th week. 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. 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.