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Efficacy and Safety of Diacerein With Inadequately Controlled Type 2 Diabetes

Common osteoarthritis treatment may be beneficial in lowering HbA1c.

The anthraquinone derivative found in cassia plants, diacerein, has been used for the symptomatic relief of osteoarthritis for many years. While the mechanism is still unclear, diacerein is believed to act as an immune modulator by inhibiting the synthesis and activity of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).

The role of inflammatory pathways in the pathogenesis of type 2 diabetes has been well-accepted in the diabetes community. The two main mechanisms responsible for the development and progression of type 2 diabetes involves defective pancreatic β-cell insulin secretion and peripheral insulin resistance. Both have immuno-inflammatory-mediated bases and involve the proinflammatory IL-1β pathway. Because of the role inflammatory pathways play in type 2 diabetes, researchers have proposed targeting these pathways as potential treatments for patients with type 2 diabetes. Currently, there has only been one study assessing the effect of diacerein in patients with type 2 diabetes. Therefore, researchers conducted a randomized controlled trial of patients with poorly controlled type 2 diabetes and high cardiovascular risk to the assess the efficacy and safety of adding diacerein to their current diabetes regimen.

This study was a single-center, randomized, 1:1, double-blinded, parallel, placebo-controlled clinical trial conducted at a university hospital over the course of 48 weeks. The primary outcome was to determine if diacerein was superior to placebo in improving glycemic control in patients with poorly controlled type 2 diabetes. Eligible patients were adults (< 75 years old) with an HbA1c between 7.5% and 9.5% stable on oral or insulin therapy. Out of 512 patients screened for the trial, 84 total participants were randomized to placebo (n=41) or diacerein (n=43). Both group’s baseline characteristics were similar and well-balanced, except for increased leukocyte counts and serum transferase levels in the diacerein group. Most of the participants were obese women using insulin, with a 10-year history of diabetes and a mean HbA1c of 8.2%. In evaluating the changes in glycemic control during treatment, the diacerein group had a lower mean HbA1c level (mean difference in change -0.35%; p=0.038) compared to the placebo group. There was a greater reduction in HbA1c at the halfway mark, 24 weeks, in comparison to week 48, with participants in the diacerein group exhibiting an HbA1c reduction of 0.78%. However, this greater reduction in HbA1c was not sustainable and at the end of the trial, patients in the diacerein group had only experienced an average HbA1c reduction of 0.35%. There were no statistically significant changes in body weight, blood pressure levels, serum lipid levels, renal function or hepatic function. Additionally, no effect on fasting plasma glucose was observed.

There are several limitations to this study. First, patients in both groups were either taking oral antidiabetic medications or insulin. Patients on insulin therapy are considered hyperglycemic resistant and typically do not show as great a reduction with add-on therapy as patients on non-insulin therapies.

Researchers could have been more selective with their participants and excluded any patients who were on insulin therapy. Second, this was a small trial with an uneven distribution of males to females (1:4) Only 43 participants were randomly selected to take diacerein, making it difficult to determine what effect the drug had on the glycemic control versus individual variability. This trial was a first step in investigating the effect diacerein has on glycemic control, but future studies are warranted. Overall, this 48-week trial showed that diacerein reduced HbA1c by 0.35%. There were very few adverse reactions reported and the most common complaint was diarrhea. Diacerein as an add-on therapy to a diabetes regimen may offer some benefit, but larger randomized controlled trials evaluating the long-term cardiorenal safety and efficacy profile are needed.

Practice Pearls:

  • Participants in the Diacerein arm of the study saw an average HbA1c reduction of 0.35%.
  • The majority of participants in this trial were on insulin-therapy, therefore it may be possible that greater HbA1c reduction could be seen in patients on non-insulin therapies.
  • Diacerein was well-tolerated without serious adverse events; the main complaint was diarrhea.

Cardoso, Claudia RL, et al. “Efficacy and Safety of Diacerein in Patients With Inadequately Controlled Type 2 Diabetes: A Randomized Controlled Trial.” Diabetes Care (2017): dc170374.

 

Jessica Lambert, University of South Florida College of Pharmacy, Doctor of Pharmacy Candidate 2018