Efficacy and Safety of Lipase Inhibitor Orlistat in Japanese with Excessive Visceral Fat Accumulation: 24-Week, Double-Blind, Randomized, Placebo-Controlled Study

摘要

IntroductionOrlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat accumulation in Japanese subjects. Therefore, this comparative, placebo-controlled, double-blind, randomized study aimed to evaluate the efficacy and safety of orlistat in Japanese participants with excessive visceral fat accumulation and without dyslipidemia, diabetes mellitus, and hypertension (metabolic diseases).MethodsThe study population included Japanese participants with excessive visceral fat accumulation (waist circumference85cm in males and90cm in females, which corresponds to a visceral fat area of 100cm(2)) and without metabolic diseases. Following a 12-week observation term, participants were randomized to the orlistat 60mg group (n=100) or placebo group (n=100). Both drugs were administered orally three times daily for 24weeks. Participants were also counseled to improve their diet and to maintain exercise throughout the study. Visceral fat area, subcutaneous fat area, waist circumference, body weight, body mass index, adverse reactions, laboratory tests, and blood pressure were regularly assessed.ResultsVisceral fat area, waist circumference, and body weight were significantly reduced in the orlistat group (meanstandard error, -13.501.52%, -2.510.25%, and -2.79 +/- 0.30%, respectively) compared to the placebo group (-5.45 +/- 1.50%, -1.55 +/- 0.26%, and -1.22 +/- 0.28%, respectively) at the last assessment. The main adverse reactions were defecation-related symptoms including oily spotting and flatus with discharge, resulting from the pharmacological effects of orlistat. Most adverse reactions were mild, and none were serious or severe.Conclusion4"Orlistat administration reduced visceral fat area, waist circumference, and body weight in Japanese participants with excessive visceral fat and without metabolic diseases. In addition, safety was confirmed with a tolerable profile. Orlistat may be useful to reduce excessive visceral fat accumulation when used in combination with diet and exercise.Trial Registration6"Japan Pharmaceutical Information Center identifier, JapicCTI-184005.Funding5"Taisho Pharmaceutical Co., Ltd.