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Drug Safety 2008Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat... (Review)
Review
Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.
Topics: Anti-Obesity Agents; Drug Interactions; Humans; Intestines; Lactones; Lipase; Nonprescription Drugs; Orlistat
PubMed: 18095746
DOI: 10.2165/00002018-200831010-00005 -
Pharmacotherapy Mar 2000Orlistat, a weight-loss agent with a novel mechanism of action, recently was approved by the Food and Drug Administration for the treatment of obesity. It inhibits... (Review)
Review
Orlistat, a weight-loss agent with a novel mechanism of action, recently was approved by the Food and Drug Administration for the treatment of obesity. It inhibits gastric and pancreatic lipases in the lumen of the gastrointestinal tract to decrease systemic absorption of dietary fat. In several trials lasting up to 2 years, orlistat was more effective than diet alone for weight reduction and maintenance of lost weight. Orlistat treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and insulin concentrations. The major adverse effects are gastrointestinal, usually occur early in therapy, and tend to decrease with continued treatment. Because orlistat may decrease the absorption of fat-soluble vitamins, a standard multiple-vitamin supplement is recommended daily during therapy to prevent abnormalities in vitamin serum concentrations. The potential for severe gastrointestinal discomfort and the modest degree of weight loss may limit the agent's clinical utility. Its long-term safety and effectiveness for weight maintenance, cost-effectiveness of treatment, and overall reduction in obesity-related morbidity and mortality remain to be determined.
Topics: Anti-Obesity Agents; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat; Randomized Controlled Trials as Topic
PubMed: 10730683
DOI: 10.1592/phco.20.4.270.34882 -
Drugs Aug 1998Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated... (Clinical Trial)
Clinical Trial Review
Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.
Topics: Drug Tolerance; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat
PubMed: 9711448
DOI: 10.2165/00003495-199856020-00007 -
Heart Disease (Hagerstown, Md.) 2000Obesity is a risk factor for cardiovascular disease. Orlistat is a gastric and pancreatic lipase inhibitor indicated for the management of obesity. It is the first... (Review)
Review
Obesity is a risk factor for cardiovascular disease. Orlistat is a gastric and pancreatic lipase inhibitor indicated for the management of obesity. It is the first antiobesity agent that is not a centrally acting appetite suppressant; instead, it decreases absorption of dietary fat in the gastrointestinal tract. The effects of orlistat on weight loss, weight regain, and on a number of obesity-related risk factors have been assessed in large clinical trials of 1 to 2 years' duration. Compared with subjects who received placebo and a hypocaloric diet alone, weight loss of at least 5 to 10% of initial body weight was observed in a significantly larger number of subjects who were treated with orlistat plus a hypocaloric diet during the first year of treatment. Subjects who received orlistat 120 mg three times daily regained significantly less weight than subjects who received placebo during the second year of treatment. In addition, orlistat was found to have favorable effects on blood pressure and concentrations of serum lipid, glucose, and insulin. Gastrointestinal events are the most common adverse effects experienced by patients who received orlistat; however, most of these events were mild to moderate in intensity, transient in duration, and decreased considerably during the second year of treatment.
Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Lactones; Obesity; Orlistat; Time Factors
PubMed: 11728255
DOI: No ID Found -
Medicine Sep 2023Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity.... (Review)
Review
Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity. In addition to being regarded as a slimming drug, a growing number of studies in recent years have suggested that orlistat has anti-tumor activities, while the underlying mechanism is still not well elucidated. This paper reviewed recent pharmacological effects and mechanisms of orlistat against tumors and found that orlistat can target cancer cells through activation or suppression of multiple signaling pathways. It can induce tumor cells apoptosis or death, interfere with tumor cells' cycles controlling, suppress fatty acid synthase activity, increase ferroptosis, inhibit tumor angiogenesis, and improve tumor cells glycolytic. Thus, this review may shed new light on anti-tumor mechanism and drug repurposing of orlistat, and anti-tumor drug development.
Topics: Humans; Orlistat; Obesity; Apoptosis; Drug Repositioning; Glycolysis
PubMed: 37682175
DOI: 10.1097/MD.0000000000034671 -
The American Journal of Clinical... Apr 2023Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance.
OBJECTIVES
This study aimed to compare the effects of orlistat or an experimental high-protein/lower-carbohydrate diet with a control diet in Asian patients with obesity and MAFLD.
METHODS
A total of 118 Asian patients with obesity and MAFLD confirmed with MRI-based proton density fat fraction with Dixon sequence were enrolled and allocated to the control group, the orlistat group, or the experimental diet group for 24 wk. The primary endpoint was the relative change in liver fat content (LFC) assessed by MRI-based proton density fat fraction.
RESULTS
A total of 118 subjects with obesity and MAFLD were randomly assigned to the control group (n = 39), the orlistat group (n = 40), or the experimental diet group (n = 39). All 3 groups demonstrated improvement in liver steatosis at wk 24. The absolute decrease in LFC in the orlistat group was 9.1% and 5.4% in the experimental diet group, both significantly higher than that in the control group (P < 0.05). The relative reduction in LFC was 30.2% in the experimental diet group, which was significantly higher than the 12.2% observed in the control group (P = 0.01).
CONCLUSIONS
Orlistat and the experimental diet group reduced liver steatosis compared to the control group. This trial was registered at Chinese Clinical Trial Registry (ChiCTR-1900027172). http://www.chictr.org.cn.
Topics: Humans; Orlistat; Protons; Anti-Obesity Agents; Lactones; Obesity; Diet; Fatty Liver; Liver Diseases
PubMed: 36781126
DOI: 10.1016/j.ajcnut.2023.02.008 -
Intensive & Critical Care Nursing Oct 1999The introduction of orlistat (Roche, UK) at the end of last year received considerable media coverage and was heralded in some quarters as the 'quick fix' for those... (Review)
Review
The introduction of orlistat (Roche, UK) at the end of last year received considerable media coverage and was heralded in some quarters as the 'quick fix' for those wishing to lose weight without the pain of dieting. This description is far from accurate but treatment with orlistat may have a role in patients for whom obesity is a serious and even life-threatening condition.
Topics: Anti-Obesity Agents; Drug Monitoring; Drug Prescriptions; Humans; Lactones; Obesity; Orlistat; Patient Selection
PubMed: 10808826
DOI: 10.1054/iccn.1999.1445 -
Drugs Oct 1999Orlistat is a novel non-systemic treatment for obesity. The drug inhibits lipases in the gastrointestinal tract, preventing the absorption of approximately 30% of... (Review)
Review
UNLABELLED
Orlistat is a novel non-systemic treatment for obesity. The drug inhibits lipases in the gastrointestinal tract, preventing the absorption of approximately 30% of dietary fat. Pharmacodynamic and dose-finding studies have established that a 120 mg dose of orlistat 3 times daily (with each main meal) is optimal. Controlled studies have established that orlistat 120 mg 3 times daily for 1 year, in conjunction with a hypocaloric diet, enables weight reduction of 7.9 to 10.2% in obese non-diabetic individuals. In 1 study the reduction was 6.2% in obese patients with type 2 diabetes. Orlistat 120 mg 3 times daily was significantly more effective than placebo (also given in conjunction with a hypocaloric diet) in these studies. The drug was also significantly more effective than placebo in 2-year randomised double-blind studies involving >2000 patients. During the second year of treatment, when patients were switched from a hypocaloric diet to a eucaloric diet, orlistat recipients regained significantly less weight than placebo recipients. Orlistat appears to improve lipid profiles in non-diabetic obese patients, reducing levels of total cholesterol and low density lipoprotein cholesterol. In a study of patients with obesity associated with type 2 diabetes, patients treated with orlistat lost more weight and had improved serum lipid profiles compared with placebo recipients. In addition, orlistat-treated patients achieved significant improvements in glycaemic control, enabling dosages of antidiabetic drugs to be reduced. Long term (1 to 2 years) tolerability data from 2038 patients in placebo-controlled trials revealed that the drug was generally well tolerated. The most commonly reported adverse events were related to decreased fat absorption and included oily faecal spotting, flatus with discharge, faecal urgency and oily stool. Systemic adverse events attributable to orlistat were negligible.
CONCLUSION
Orlistat in conjunction with a hypocaloric diet has been shown to induce clinically significant weight loss in keeping with current guidelines for the management of obesity. This, together with its acceptable tolerability profile and lack of systemic adverse events, make it an attractive option in the treatment of obesity. The drug may have a positive effect on obesity-associated cardiovascular risk factors and type 2 diabetes.
Topics: Anti-Obesity Agents; Clinical Trials as Topic; Humans; Lactones; Obesity; Orlistat
PubMed: 10551441
DOI: 10.2165/00003495-199958040-00015 -
Expert Opinion on Drug Safety Nov 2009Obesity has rapidly become a life-threatening epidemic worldwide. There are a plethora of obesity-related co-morbidities and complications that increase morbidity,... (Review)
Review
BACKGROUND
Obesity has rapidly become a life-threatening epidemic worldwide. There are a plethora of obesity-related co-morbidities and complications that increase morbidity, mortality and cost of care associated with obesity. Orlistat is approved for the treatment of obesity and has been evaluated both in obesity and in the several obesity-related co-morbidities.
OBJECTIVE
The purpose of this article is to provide detail of the pharmacotherapeutic role of orlistat in obesity, describe orlistat and its pharmacological properties, critique the evidence for orlistat's use in obesity and obesity related co-morbidities, and define the role of orlistat in clinical practice.
METHODS
A thorough, all-inclusive literature search was conducted to isolate clinical trials, case reports and meta-analyses evaluating the safety and efficacy of orlistat in various patient populations.
RESULTS
Orlistat's unique mechanism of action, beneficial effects on multiple co-morbidity surrogates and relatively mild adverse effect and drug interaction profile position it favorably as the first option for pharmacotherapy in comprehensive obesity management of adults and children.
Topics: Animals; Anti-Obesity Agents; Drug Approval; Drug Interactions; Humans; Lactones; Meta-Analysis as Topic; Nonprescription Drugs; Obesity; Orlistat; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration
PubMed: 19998527
DOI: 10.1517/14740330903321485 -
The Annals of Pharmacotherapy Mar 2001To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of... (Review)
Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of obesity.
DATA SOURCES
English-language articles were identified from MEDLINE (1966-July 2000), Roche Laboratories, organizational guidelines, National Institutes of Health and Food and Drug Administration Web sites, and Doctor's Guide online. Key words included obesity, orlistat, and lipase inhibitors. References were also identified from reference sections of published articles.
STUDY SELECTION AND DATA EXTRACTION
Prospective, randomized, double-blind, placebo-controlled, human trials were selected for review and discussion.
DATA SYNTHESIS
Orlistat is the first agent in the lipase inhibitor class of antiobesity drugs. Orlistat is minimally absorbed and has been shown to reduce body weight by inhibiting absorption (by approximately 30%) of ingested dietary fat. Safety and efficacy have been established in one- and two-year double-blind, placebo-controlled trials; adverse effects were primarily, and almost exclusively, gastrointestinal. Due to its ability to block fat absorption, orlistat also has the capability to inhibit absorption of fat-soluble vitamins. Therefore, a daily multiple vitamin is recommended while taking orlistat.
CONCLUSIONS
By inhibiting fat absorption, orlistat offers a new treatment modality for weight loss and maintenance. Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia. However, further studies during postmarketing surveillance are needed to fully establish orlistats long-term benefits and safety. Orlistat should be considered a useful adjunctive therapy for weight loss and maintenance in obese patients (i.e., body mass index > or = 30 kg/m2 or > or = 27 kg/m2 if other risk factors are present) committed to lifestyle changes including diet, exercise, and behavioral modification.
Topics: Animals; Anti-Obesity Agents; Clinical Trials as Topic; Humans; Lactones; Obesity; Orlistat
PubMed: 11261530
DOI: 10.1345/aph.19412