Reduction of Excessive Visceral Fat and Safety with 52-Week Administration of Lipase Inhibitor Orlistat in Japanese: Long-Term Clinical Study

Introduction Orlistat 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 (VF) accumulation in Japanese individuals. Therefore, this study aimed to analyze the efficacy and safety of 52 weeks of orlistat administration in Japanese individuals. Methods Orlistat 60 mg was administered orally three times daily for 52 weeks to Japanese participants with excessive VF accumulation and without dyslipidemia, diabetes mellitus, and hypertension (metabolic diseases). Participants were also counseled to improve their diet and to maintain exercise habits. We defined excessive VF accumulation as a waist circumference (WC) of ≥ 85 cm for males and ≥ 90 cm for females, which corresponds to a VF area of 100 cm 2 . Adverse reactions, clinical laboratory tests, VF, WC, body weight (BW), etc., were monitored throughout the study period. Results VF, WC, and BW were significantly reduced at week 52 from baseline; the mean ± standard error rate of change was − 21.52% ± 1.89%, − 4.89% ± 0.45%, and − 5.36% ± 0.56%, respectively, and continued to reduce throughout the 52 weeks; these significantly reduced at whole term compared with baseline. Most adverse reactions were defecation-related symptoms such as oily spotting and flatus with discharge (flatus with small amounts of stool or oil) due to the pharmacologic effects of the lipase inhibitor. These symptoms were mostly mild, reversible, and recognizable by the participants; none were serious or severe. No participants discontinued by medical judgment about adverse reactions, and the drug could be administered continuously. Conclusion VF, WC, and BW were reduced from week 4 to week 52, indicating the effect of long-term orlistat administration. Moreover, it was well tolerated with an acceptable safety profile. Long-term administration of orlistat may be efficacious in reducing VF accumulation with safety when used in combination with diet and exercise. Trial Registration This study is registered with the Japan Pharmaceutical Information Center (identifier: JapicCTI-184004). Funding Funding for this study was provided by Taisho Pharmaceutical Co., Ltd.