Discussion
The effect of orlistat on serum uric acid level has been examined in several studies and the results were inconsistent. To our knowledge, the present study is the first meta-analysis on the effect of orlistat on serum uric acid level. By analyzing the data from 7 clinical trials (9 dataset) involving 1786 participants, we found that orlistat could significantly decrease serum uric acid level in comparison with placebo/control.
Our finding of the effect of orlistat on serum uric acid level improvement was supported by evidence from previous trials [20, 21] and in the first group of one trial [25]. However, in contrast to our results, some trials revealed that orlistat is caused decrease serum uric acid but not significantly [22, 24] and in the first group of one trial [26]. Also one trial [23] and in the second group of two trials [25, 26] were showed that increase serum uric acid after orlistat therapy.
When stratifying by health status, this meta-analysis shows a consistent protective effect of orlistat on serum uric acid in patients with hypercholesterolemia than other disease like metabolic syndrome, PCOS and NAFLD. Although we did not find any significant change of serum uric acid after orlistat therapy studies with sample size <100 but beneficial effect of orlistat on serum uric acid was observed in studies with sample size >100. When we classified based on the duration of the studies, a significant positive effect on serum uric acid levels was observed during 6 month. It is notable that in a group of participants who received a low-calorie diet with orlistat, the significant reduction was found in serum uric acid in comparison to other mentioned subgroups. Also, meta-regression suggested that significant relationships were not found between orlistat and serum uric acid in duration of intervention.
The potential mechanism of uric acid-lowering effect of orlistat is still unclear and further studies are warranted. The link between gout, obesity and metabolic syndrome is well‐established. Post‐bariatric surgery weight loss results in a significant and sustained improvement in SUA levels up to the third postoperative year, as well as a reduction in the incidence of gout attacks[27]. Weight loss (>5 kg) achieved by therapeutic lifestyle changes or bariatric surgery has been reported to decrease urate levels by 8.0 to 10.0 μmol/dl [8].Therefore, one of the possible mechanisms of orlistat for reducing uric acid is its weight loss effect. One meta-analysis also showed that SUA levels are significantly associated with dyslipidemia, and this association is impacted by age and gender [28]. The other meta-analysis demonstrated obesity is associated with multiple CVD risk factors such as dyslipidemia. The mechanism by which weight loss medications impact CVD risk reduction could be a direct effect of these agents or merely an effect of weight reduction itself. In addition, the mechanism of action of the medications are not directly anti-inflammatory, and do not directly modify insulin sensitivity, blood pressure or the lipid profile. Weight loss has been noted to modify risk factors via modifying the lipid profile. Thus, it is most likely that the benefit on cardiovascular disease from these therapies is via weight reduction and not direct medication effect. Pharmacological weight loss therapy may be a valuable treatment option to reduce CVD risk in patients with obesity [29]. Further research is needed to clarify the effects these therapies on overall mortality and evaluate the mechanisms by which these medications reduce CVD risk factors and mortality [29]. The findings of the prospective cohort study suggest that higher level of high-sensitivity CRP is an independent risk factor for hyperuricemia in Chinese, especially in women[30].While in one study significant associations between baseline SUA levels, and high-sensitivity C-reactive protein were identified but a decrease in SUA level from baseline to 24-week follow-up was not associated with significant changes in high-sensitivity C-reactive protein [31]. One meta-analysis study was demonstrated orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP [32]. So it’s not clear if orlistat can reduce serum uric acid by lowering CRP.