The role of orlistat in weight management.

Marks S.

Monash Medical Centre, Melbourne, Victoria.

BACKGROUND: Most antiobesity drugs act centrally to reduce appetite or increase satiety. Orlistat is the first in a new class of drugs targeted at a single dietary component, in this case dietary fat. OBJECTIVE: To review the clinical actions and efficacy of orlistat and to discuss its place in overall weight management. DISCUSSION: Orlistat is best used in long term weight management as an adjunct to dietary modification and increased physical activity. The reduction in fat absorption results in a slow but sustained weight reduction and improved metabolic parameters such as reduced total, and LDL cholesterol. Side effects are minimised by maintaining a low fat diet.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11355219&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Orlistat: new preparation. No hurry . . .

[No authors listed]

(1) Treatments for obesity are disappointing. None has yet shown an effect on morbidity and mortality. Non drug treatments are poorly assessed. Stable long-term weight loss necessitates long-term management. (2) Orlistat, a gastrointestinal lipase inhibitor, is indicated, in combination with a low-calorie diet, for the management of obesity. (3) The assessment file is rather bulky and methodologically sound, at least in terms of the "weight loss" end point. (4) During medium-term trials (12-24 months), orlistat administered at a dose of 120 mg three times a day and combined with dietary intervention had a moderate positive impact on body weight (-3.5 kg on average). (5) No longer-term trials have been done. (6) It is not known whether this drug affects morbidity and mortality linked to obesity. (7) In clinical trials there was an increase in the frequency of breast cancer among patients treated with orlistat. This potential risk is currently being assessed in a specific trial. (8) Gastrointestinal adverse effects are frequent. (9) Treatment is costly.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11503834&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Incorrect use and limited weight reduction of orlistat (Xenical) in clinical practice. A cohort study.

Beermann B, Melander H, Sawe J, Ulleryd C, Dahlqvist R.

Medical Products Agency, Uppsala, Sweden. bjorn.beermann mpa.se

OBJECTIVE: To study the prescribing of the antiobesity drug orlistat in relation to the approved indication and its weight-reducing effect in clinical practice during the first 3 months of treatment. METHODS: Anonymous postal questionnaire survey to prescribers of orlistat concerning a random sample of 1000 of 20,000 prescriptions. PARTICIPANTS: Useful information was obtained for 789 patients. SETTING: Primary and secondary care in Sweden. MAIN OUTCOME MEASURES: Beginning and continued treatment according to the approved indication. Dropout from treatment. Weight loss during treatment. RESULTS: Four percent of the patients were prescribed orlistat despite having a body mass index (BMI) less than 28 kg/m2. Only 24% of the patients had a diet period with a weight loss of 2.5 kg or greater before the start of therapy. Half of the patients with a weight loss of less than 5% after 3 months continued the treatment. Ten percent gained weight or had no weight loss at all while 43% lost less than 5% in weight. At least one-quarter of the patients stopped the treatment within the observation period. CONCLUSION: Orlistat was not prescribed according to the approved indication in the majority of cases. The dropout rate was high and most patients had minor gain from the treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11549209&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function.

van Heek M, Farley C, Compton DS, Hoos L, Davis HR.

CNS/CV Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey, NJ 07033, USA. margaret.vanheek spcorp.com

1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and/or rat to determine whether ezetimibe would affect the absorption of molecules other than free cholesterol, namely cholesteryl ester, triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid. In addition, to determine whether exocrine pancreatic function is involved in the mechanism of action of ezetimibe, a biliary anastomosis model, which eliminates exocrine pancreatic function from the intestine while maintaining bile flow, was established in the rat. 3. Ezetimibe reduced plasma cholesterol and hepatic cholesterol accumulation in cholesterol-fed hamsters with an ED(50) of 0.04 mg kg(-1). Utilizing cholesteryl esters labelled on either the cholesterol or the fatty acid moiety, we demonstrated that ezetimibe did not affect cholesteryl ester hydrolysis and the absorption of fatty acid thus generated in both hamsters and rats. The free cholesterol from this hydrolysis, however, was not absorbed (92 - 96% inhibition) in the presence of ezetimibe. Eliminating pancreatic function in rats abolished hydrolysis of cholesteryl esters, but did not affect the ability of ezetimibe to block absorption of free cholesterol (-94%). Ezetimibe did not affect the absorption of triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid in rats. 4. Ezetimibe is a potent inhibitor of intestinal free cholesterol absorption that does not require exocrine pancreatic function for activity. Ezetimibe does not affect the absorption of triglyceride as a pancreatic lipase inhibitor (Orlistat) would, nor does it affect the absorption of vitamin A, D or taurocholate, as a bile acid sequestrant (cholestyramine) would.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11564660&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Principles for enhanced recruitment of subjects in a large clinical trial. the XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study experience.

Torgerson JS, Arlinger K, Kappi M, Sjostrom L.

Department of Body Composition and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.

In most clinical trials it is problematic to recruit enough patients within a reasonable time period. Prolonged or inefficient recruitment or both can have negative scientific and economic consequences. The XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study is an ongoing randomized, double-blind, placebo-controlled, prospective, multicenter trial investigating whether orlistat combined with hypocaloric diet and moderate physical exercise can reduce the incidence of diabetes in obese subjects. To implement the XENDOS protocol and recruit the study patients, we designed a system for centralized patient recruitment and centralized scheduling of patients and staff at the 22 collaborating centers. The recruitment and inclusion phase was divided into a series of different consecutive examinations of increasing complexity. Relatively simple initial examinations enabling a large throughput of patients were followed by more detailed examinations of fewer subjects, by then known to fulfil some of the study-specific requirements. With the aid of object-oriented techniques, the software was modularized to enable concurrent engineering. We also selected a structure where plug-in modules handling specific tasks could be added to the system as needed. The design was supported by a flow-oriented view of the progress of the patients through the study. With this overall solution we managed to include 3305 subjects (98.8% of the requested number) within less than 4 months. The sex distribution (44.8% men) and the number of patients with impaired glucose tolerance (IGT), (21.1%) were in close accordance with, or far better than, the requirements of the protocol (45% men, at least 10% IGT patients). The basic design of the XENDOS information system can be adapted to fulfil the requirements of other study protocols within the fields of obesity, diabetes, hypertension, coronary heart disease, etc. Shortening the recruitment and inclusion phase of large clinical trials is of great value both to be medical society and the pharmaceutical industry.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11578785&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)