Fibrate therapy and circulating adiponectin concentrations: A systematic review and meta-analysis of randomized placebo-controlled trials

• Plasma adiponectin levels are inversely associated with cardiovascular outcomes.
• This study reviewed clinical trials on the impact of fibrates on adiponectin levels.
• Fibrate therapy significantly increases circulating adiponectin levels.
• The observed effect size was significant and robust in sensitivity analyses.
• Elevation of plasma adiponectin may be regarded as a pleiotropic effect of fibrates.

BackgroundSeveral lines of evidence have indicated the insulin-sensitizing, anti-diabetic and anti-atherosclerotic properties of adiponectin, as well as the inverse association between circulating levels of this adipokine and development of cardiovascular outcomes. Improvement of adiponectin status has been reported as a pleiotropic effect of fibrate therapy, but the findings have not been conclusive.ObjectiveTo systematically review and meta-analyze available evidence from randomized placebo-controlled trials (RCTs) on the impact of fibrate therapy on circulating levels of adiponectin.MethodsA comprehensive literature search in Medline was carried out to identify RCTs comparing the effect of fibrate therapy vs. placebo on circulating concentrations of adiponectin. A meta-analysis of eligible studies was performed using a random-effects model. Quality assessment, sensitivity analysis and publication bias evaluations were conducted using standard methods.ResultsTwelve RCTs comprising 443 cases and 437 controls met the selection criteria for systematic review, out of which 9 RCTs (399 cases and 401 controls) were included in the meta-analysis. Quantitative data synthesis revealed a significant effect for fibrate therapy in increasing circulating adiponectin levels (weighed mean difference: 0.38 μg/mL; 95% confidence interval: 0.13–0.63 μg/mL; p = 0.003). The effect size remained statistically significant when restricting the analysis to fenofibrate trials [0.31 (0.21–0.42) μg/mL; p < 0.00001). The observed effect was robust in sensitivity analyses and independent of fibrate dose. Imputation for potential missing studies led to the estimation of a greater effect size for fibrate therapy [0.53 (0.24–0.82) μg/mL].ConclusionThe present meta-analysis suggests that fibrate therapy increases circulating levels of adiponectin. Whether increase in adiponectin levels contributes to reduction of cardiovascular effects in subjects with dyslipidemia treated with fibrates merits further investigation.