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.