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    Home > Medical News > Latest Medical News > Reexamination of the efficacy and safety of orlistat

    Reexamination of the efficacy and safety of orlistat

    • Last Update: 2019-02-20
    • Source: Internet
    • Author: User
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    "Three jins of new year's fat" is a problem that many Chinese have to face after "pushing the cup to change the cup" and "indulge in delicious food" during the Spring Festival Therefore, in addition to quickly entering the working state, weight loss has also been put on the agenda by many office workers As we all know, orlistat is the only officially recognized weight-loss drug in China Its good safety and effectiveness have been fully verified in a large number of clinical trials It is a little regrettable that most of the above clinical trials take the overweight and obese people in Europe and the United States as subjects Only two randomized, double-blind and controlled clinical trials published in the Chinese Journal of Endocrinology and metabolism by Shi Yifan et al Investigated and confirmed the safety and effectiveness of orlistat on the overweight and obese people in China However, neither of the above two studies examined orlistat's effect on the overweight and obese people in China The effect of body fat was studied for 24 weeks Most of the other domestic studies related to orlistat are observational studies, which reduces the effectiveness of its proof Recently, two clinical trials carried out in Japan published in the first issue of Volume 36, 2019 of advanced theories further confirmed the safety and effectiveness of orlistat for overweight and obese people in East Asia, and also confirmed that orlistat can significantly improve their fat accumulation status, thus adding new evidence for orlistat's clinical application The two Japanese clinical trials were funded by Dazheng pharmaceutical and registered in the Japanese drug information center Among them, the randomized double-blind placebo-controlled clinical trial with Registration No japiccti-184005 included 200 Japanese overweight / obese people (male waist ≥ 85CM, female waist ≥ 90cm, both equal to visceral fat area ≥ 100cm2) who had excessive accumulation of visceral fat and had not complicated with recess disease After 12 weeks of observation, orlistat 60mgtid or placebo were added to the diet with low calorie and moderate exercise The main efficacy results after 24 weeks of treatment are shown in the table below The most common adverse reactions in this study included oily spots and fecal exhaust, which were all caused by the mechanism of orlistat, and most of them were mild Another 52 week open label, single group and non control trial with registration number of japiccti-184004 also took Japanese overweight and obese people with excessive accumulation of body fat as the study object After 52 weeks of continuous treatment with orlistat 60mgtid on the basis of low calorie diet and moderate exercise, the decrease rate of body fat, waist circumference and weight relative to the baseline was − 21.52% ± 1.89% respectively And − 4.89% ± 0.45% and − 5.36% ± 0.56% respectively, and the above parameters kept a continuous downward trend throughout the treatment The adverse reactions of orlistat observed in the 52 week clinical trial were similar to those observed in the 24 week clinical trial They were oil spots and fecal exhaust caused by the mechanism of orlistat action The adverse reactions were mild and reversible, and no subjects stopped treatment due to adverse reactions [extended analysis] 1 New weight-loss drugs are generally considered in Japan as a country with relatively light risk of obesity Therefore, 22.0kg/m2 < BMI < 35kg / m2 is taken as the inclusion criteria of the above two clinical trials Although Dazheng pharmaceutical and GlaxoSmithKline reached an agreement on the cooperation and development of orlistat as early as 2009, its new drug application in Japan has not made progress Although the results of the clinical trials were published in the Journal of advanced therapeutics, the official website of Dazheng pharmaceutical did not make a statement on whether or not to start the declaration work of orlistat In September 2013, Japan's Ministry of health, labor and welfare approved cetilistat, another lipase inhibitor weight-loss drug jointly developed by Takeda Pharmaceutical Co., Ltd and norgine pharmaceutical However, cetilistat has not been included in the medical insurance due to its poor weight-loss effect (about 2% weight loss), so it is not listed in Japan In July 2018, Takeda announced the termination of its cooperation with norgine, which ultimately dashed cetilistat's hopes of listing in Japan In terms of several other oral weight-loss drugs approved by FDA in recent years, none of the relevant companies disclosed the declaration, transfer and listing dynamics involving Japan 2 Overall effectiveness of orlistat (1) weight loss effect the official website of orlistat of GlaxoSmithKline points out that adding orlistat 60mgtid treatment on the basis of diet control and moderate exercise can reduce 1.5% more weight than simply diet control and moderate exercise Bray's review published in lancet magazine, Vol 87, No 10031, 2016 rated orlistat's weight loss effect as "moderate" Specifically, according to FDA instructions, the weight loss rate of subjects in orlistat 120mgtid group and placebo group was - 6.1% and - 2.6% respectively A meta-analysis of 33 randomized controlled clinical trials published by sahebkara et al In the Journal of Pharmacol res 2017, Volume 122, showed that compared with placebo, orlistat significantly reduced the weight of overweight / obese people, with a weighted mean difference (hereinafter referred to as WMD) of - 2.12kg, P < 0.001 (2) Many clinical trials have proved that orlistat can significantly improve the blood lipid metabolism of overweight / obese people In summary, a meta-analysis of 33 randomized controlled clinical trials published by sahebkara et al In Volume 122, 2017, showed that WMD of the effect of orlistat and placebo on the improvement of blood lipid parameters was - 0.30mmol/l (total cholesterol, P < 0.001), - 0.27mmol/l (LDL cholesterol, P < 0.001), - 0.034mmol/l (HDL cholesterol, P < 0.001) and - 0.09mmol/l (glycine), respectively Oleotriene, P < 0.001), but orlistat had no significant effect on lipoprotein (a) It is worth noting that several tests (such as erdmann et al Aliment pharmaceutical their 2004jun1; 19 (11): 1173-9.) have confirmed that orlistat's lipid-lowering effect is independent of its weight-loss effect (3) A number of clinical trials confirmed that orlistat can significantly reduce the diastolic and systolic blood pressure of overweight / obese people In summary, a meta-analysis of 27 randomized controlled trials published by sahebkara et al In jamsochypertens Journal, Vol 12, No 2, 2018 showed that the WMD of orlistat in reducing systolic and diastolic blood pressure compared with placebo was - 1.15mmhg (95% CI: - 2.11, - 0.19) and - 1.07mmhg (95% CI: - 1.69, - 0.45), respectively (4) Several clinical trials have confirmed that orlistat can significantly improve the blood glucose metabolism of overweight / obese patients with type 2 diabetes 8 mmol / L, P < 0.001) 。 (5) Many clinical trials confirmed that orlistat can significantly improve adiponectin and other obesity related blood biochemical indicators In summary, a meta-analysis of 12 randomized, controlled clinical trials, published in brjclinpharmacol Vol 81, No 5, 2016, by derosag et al Showed that compared with placebo, orlistat significantly increased adiponectin levels (WMD = 19.18%, 95% CI: 5.80,32.57, P = 0.005) and significantly reduced leptin levels (WMD = - 13.24%, 95% CI: - 20.69), -5.78, P = 0.001) and C-terminal reactive protein (WMD: - 11.52%, 95% CI: - 16.55, - 6.49, P < 0.001) (6) Effective type 2 diabetes, dyslipidemia and hypertension are common complications of overweight / obesity in the population with special complications Therefore, a large number of orlistat clinical trials have included a considerable number of overweight / obese people with the above complications as subjects ① Polycystic ovary syndrome (PCOS) Graffsk et al Published in the Journal intjclin practice, Vol 70, No 6, 2016, included 9 clinical trials (including 3 prospective non randomized trials and 6 randomized trials) The results showed that orlistat and DMG had similar positive effects on BMI, HOMA and testosterone levels of PCOS patients, and their WMD was - 0.65% (95% CI: - 2.03 ~ 0.73), - 3.60% (95% CI: - 16.99) ~9.78), - 2.08% (95% CI: - 13.08-8.93) and - 5.51% (95% CI: - 22.27-11.26) Recently, the results of a randomized controlled trial published by researchers from Capital Medical University of China in No 6, volume 297, arch syncoloobstet Journal 2018 confirmed that the addition of orlistat (do group), metformin (DM group) and orlistat + metformin (DOM group) on the basis of Diane-35 (ethinylestradiol and cyproterone tablets) and the treatment of alone Diane-35 (D group) could be significant To improve the serum testosterone, sex hormone binding globulin (SHBG) and androgen index (SHBG) in PCOS patients The levels of DHEA-S and androstenedione in all groups except group D were significantly lower than those in DOM group The body fat volume and body fat rate of do group and DOM group were significantly reduced Chinese diagnosis and treatment guidelines for polycystic ovary syndrome (2018 version) prepared by the endocrinology group and guidance expert group of Obstetrics and Gynecology branch of Chinese Medical Association recommended that orlistat be used for weight control of PCOS patients ② Nonalcoholic fatty liver In a paper published in biomedrep Journal, Vol 9, No 1, 2018, researchers from Xuzhou Medical University in China included the meta-analysis results of three randomized controlled clinical trials and four single group trials The results showed that orlistat could significantly improve the alanine transaminase (standard mean deviation [SMD] = - 1.41) in patients with nonalcoholic fatty liver (NAFLD) or nonalcoholic steatohepatitis (NASH); ) Although the results of subgroup analysis showed that orlistat had no significant effect on NASH patients, the authors suggested that orlistat could be used as an alternative to improve liver injury The guidelines for the prevention and treatment of nonalcoholic fatty liver disease (updated in 2018) jointly prepared by the fatty liver and alcoholic liver disease group of Hepatology branch of Chinese Medical Association and fatty liver disease expert committee of Chinese Medical Association recommends that adults with BMI ≥ 30kg / m2 and adults with BMI ≥ 27kg / m2 accompanied by hypertension, T2DM, dyslipidemia and other complications may consider using orlistat and other drugs to lose weight 3 The overall safety features of orlistat although orlistat is criticized for its "embarrassing" gastrointestinal adverse reactions such as oily spots and fecal exhaust, the above adverse reactions are caused by the mechanism of orlistat inhibiting lipase activity and fat absorption, and most of them are mild to moderate, and can disappear or be relieved by themselves Since the absorption of orlistat after oral administration is very low (< 2%), there is no significant adverse effect on the circulatory system and nervous system, so Bray et al described it as one of the "safest" weight-loss drugs in their review Another safety flaw that is often criticized by the media is the risk of liver injury In May 2010 and February 2012, the US FDA and the EU EMA discussed the liver injury of orlistat (including 120mg and 60mg)
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