In this pilot study, we did not find any additional effects of Diacerein on weight loss and inflammatory variables. As mentioned above, two-way ANOVA may not be useful in this study. Therefore, we had only simple comparison by non-parametric test. The treatment group as compared to the placebo group showed a reduction in body weight (- 7.0 kg vs. 4.6 kg), BMI (- 2.51 kg/m2 vs. - 1.59 kg/m2), and waist circumference (- 7.3 cm vs. - 4.4 cm); however, there was no statistical significance between the two groups. Changes in levels of low-density lipoprotein, hsCRP, and adiponectin in the treatment group showed improvement, which were also not significant when compared to those in the placebo group. Other inflammatory markers such as white blood cells, homocysteine, fibrinogen, and TNF-α were not significantly different either.
There have been many studies of changes of the inflammation and body weight in several different body weight control programs. For instance, studies on the changes in inflammatory markers after weight reduction reported different results, which may have reflected the different study methods. One study showed that during the eucaloric phase, a low-fat, high-carbohydrate diet unfavorably influenced inflammatory markers. In contrast, ad libitum low-fat, high-carbohydrate intake caused weight loss and affected inflammatory markers favorably. Thus, the energy content of a low-fat, high-carbohydrate diet determined changes in inflammatory markers.18
Another study reported an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions and inflammation in high-risk subjects.19
In another study, no significant changes were evident in either median adiponectin or IL-10 levels after body weight reduction.20
In this study, the authors opined that the anti-inflammatory status of obesity might require prolonged periods of energy-restricted diets to revert to normal. A study in which metformin was provided for 17 weeks reported significant reduction in body weight, but not in levels of TNF-α and CRP.21
Metformin improved the plasma levels of some markers of endothelial activation and coagulation in subjects with impaired glucose tolerance, whereas it had no effect on markers of inflammation. In a study of 316 community-dwelling, older overweight or obese sedentary men and women with osteoarthritis, diet-induced weight-loss intervention resulted in significantly greater reductions in CRP, IL-6, and TNF-α than treatment not intended to reduce weight.22
In this study, CRP and IL-6 were not associated with changes in body weight. The addition of cis-9, trans-11 conjugated linoleic acid also did not produce any differences between groups in body composition in a double-blind, placebo-controlled 3-month study of 25 abdominally obese men.23
While a decrease in many inflammatory markers such as TNF-α, CRP-reactive protein and IL-6 were reported in another study, adiponectin levels were significantly higher after intervention.24
Many studies evaluating changes of inflammatory marker after different periods or regimens of weight reduction have not yielded consistent results. However, the decrease in inflammatory markers such as TNF-α, CRP, and IL-6 and increase of adiponectin level has been apparent after weight reduction.25-28
Changes in other metabolic parameters including lipid profiles, glucose level, and TNF-α were insignificant in both groups, which may be due to the small sample size. In addition, there was no adverse drug reaction in the treatment group for the 3-month intervention period.
There are some limitations to this pilot study. The main limitation concerns the small number of subjects. This may be a crucial limitation that weakens the significance of the results, but not their reality. We tried to equally allocate to each group, but there was some follow-up loss in this study for personal reasons. Furthermore, the relatively short duration of this intervention would contribute to the lack of change in inflammatory markers, as in previous studies. Another limitation is that the intervention medication we used (Diacerein, an anti-inflammatory agent that is a TNF-α and IL-1 inhibitor) is not an officially recognized agent in the regulation of inflammation in the obese. Additionally, we could not evaluate total exercise time and frequency, which are important confounding factors. Nonetheless, to our knowledge, this is the first randomized, placebo-controlled study that investigated the effect of inclusion of an anti-inflammatory agent to a traditional obesity control regimen involving medication with Sibutramine, to evaluate whether there was additional reduction of weight and of inflammatory markers. In conclusion, we did not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.