To conduct a systematic review and meta‐analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C‐reactive protein (CRP).

Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random‐effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I² index. Sensitivity analyses were conducted using the one‐study remove approach. Random‐effects meta‐regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size.

Meta‐analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: −13.24%, 95% CI: −20.69, −5.78, p = 0.001) and CRP (WMD: −11.52%, 95% CI: −16.55, −6.49, p < 0.001) following treatment with orlistat. In meta‐regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values.

Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.