Effects of Orlistat, Alone or Combined with Hypolipidemic Drugs, on Cardiovascular Risk Factors

TD Filippatos; CS Derdemezis; MS Elisaf

Disclosures

Clin Lipidology. 2009;4(3):331-341. 

In This Article

Abstract and Introduction

Abstract

Orlistat, an antiobesity drug with well-documented efficacy in weight reduction and maintenance, has beneficial effects on metabolic variables. It reduces the incidence of Type 2 diabetes in patients with impaired glucose tolerance and decreases LDL-C levels to a greater degree than expected from weight loss alone. Orlistat is a useful therapy in overweight and obese subjects with cardiovascular risk factors. The combination of orlistat with statins, fenofibrate and ezetimibe led to greater reductions of LDL-C levels compared with each monotherapy. The combination of orlistat with fenofibrate or ezetimibe also further decreased the concentration of atherogenic, small, dense LDL-C, as well as total plasma lipoprotein-associated phospholipase A2 activity, and improved several cardiovascular risk factors compared with monotherapy. However, studies investigating the combination of orlistat with other hypolipidemic drugs only included a small number of subjects with hyperlipidemia or the metabolic syndrome.

Introduction

Orlistat is a potent and specific inhibitor of intestinal lipases.[1] The intestinal lipases are responsible for the breakdown of dietary triglycerides (TGs) into fatty acids and monoglycerides, which are then absorbed by mucosal cells. The long-term efficacy of orlistat in body weight reduction and maintenance has been well documented in long-term, randomized, placebo-controlled studies.[2–6]

Orlistat works within the gut and is minimally absorbed into the systemic circulation.[7] Therefore, a small number of systemic adverse effects have been attributed to orlistat.[8] Gastrointestinal side effects may increase when orlistat is taken with a high-fat diet (> 30% total daily calories from fat) or if the recommended daily fat intake is not distributed over three meals.[9]

In this review we consider the effects of orlistat on cardiovascular disease (CVD) risk factors. Furthermore, we present the effects of the combination of orlistat with hypolipidemic drugs, which may be useful in the usual care setting.

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