Analysis of 6-month effect of orlistat administration, alone or in combination with fenofibrate, on triglyceride-rich lipoprotein metabolism in overweight and obese patients with metabolic syndrome

BackgroundOrlistat significantly reduced serum triglycerides (TG) in most clinical trials. Orlistat-induced TG reduction has not been studied to determine the factors contributing to TG alterations in clinical settings.ObjectiveWe examined the factors influencing TG reduction during orlistat administration, alone or in combination with fenofibrate, and we investigated the effects of these treatments on apolipoprotein C-II (ApoC-II) and C-III (ApoC-III) levels.MethodsPatients with the metabolic syndrome were randomly allocated to receive orlistat 120 mg three times daily (n = 28, O group), micronized fenofibrate 200 mg/day (n = 28, F group), or both (n = 27, OF group) for 6 months. Plasma ApoC-II and ApoC-III were determined by an immunoturbidimetric assay.ResultsIn the O group, we observed reductions of plasma ApoC-III (P < 0.05) and ApoC-II (P = NS) levels. Fenofibrate administration significantly reduced concentrations of ApoC-II and ApoC-III, whereas the combination of orlistat and fenofibrate had an additive effect on these apolipoproteins. There were significant in-group reductions in serum TG levels in all treatment groups. Multivariate analysis showed that in O group's baseline TG levels were independently positively correlated, whereas the baseline ApoC-II levels were negatively correlated with TG-lowering. In the F group, baseline TG levels and ApoC-III reduction were significantly and independently correlated with TG reduction. OF group's baseline TG levels and ApoC-III reduction were independently positively correlated and baseline ApoC-II levels were negatively correlated with TG-lowering.ConclusionsOrlistat-mediated TG-lowering is independently associated with baseline TG and ApoC-II levels. When orlistat is combined with fenofibrate, ApoC-III reduction is another independent contributor to TG alterations.