Orlistat

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Abstract
Orlistat (Xenical®) is a reversible inhibitor of gastric and pancreatic lipases. In conjunction with a hypocaloric diet and moderate exercise, orlistat is an effective drug for use in the management of obesity in adults with or without comorbidities. Recent data have shown that orlistat is also effective as a component of weight management strategies in obese adolescents. In addition to its well established efficacy in achieving modest weight loss, orlistat has been shown to improve glycaemic parameters in obese adults with type 2 diabetes mellitus as well as some features of the metabolic syndrome. Orlistat is generally well tolerated. Thus, orlistat is an option for the treatment of obese patients with or without type 2 diabetes and also has a role in the management of obese patients with the metabolic syndrome, associated comorbidities or concomitant disorders. Orlistat is a reversible inhibitor of gastric and pancreatic lipases; its mechanism of action results in an inhibition of dietary fat absorption of 30% at the approved dosage. It is generally associated with a loss of fat mass in obese adults and adolescents, as well as decreases in levels of the regulatory hormone leptin as patients lose bodyweight. Vitamin levels are not consistently affected with orlistat use, with only β-carotene and vitamin D and E levels shown to be significantly decreased by orlistat administration in at least one study. Mineral levels are also not affected in obese adolescent patients. Orlistat is effective in improving factors involved or implicated in the pathogenesis of cardiovascular disease. The absorption of orlistat is minimal in both healthy adult volunteers and adult obese patients. Orlistat is not extensively metabolised, with 83% of excreted orlistat found to be intact drug. Accumulation of orlistat is minimal in both short-and long-term studies. Orlistat is excreted primarily via the faeces. Because orlistat is minimally absorbed, it has a generally favourable drug-interaction profile. Only the pharmacokinetics of ciclosporin (cyclosporin) and amiodarone have been shown to be affected by coadministration with orlistat. The bioavailability of oral contraceptives in women receiving orlistat who experience severe diarrhoea may be reduced. In numerous randomised, double-blind, placebo-controlled multicentre studies in obese adult patients, orlistat has been shown to be significantly more effective than placebo in reducing weight. Orlistat is also effective in producing modest weight loss in obese adolescent patients and in patients with additional disorders, such as type 2 diabetes and the metabolic syndrome. Several metabolic parameters are consistently improved after orlistat treatment; in patients with type 2 diabetes, mean levels of postprandial glucose and glycosylated haemoglobin are decreased. Orlistat treatment enables some patients with type 2 diabetes to decrease or discontinue their antidiabetic medication, or be reclassified to either impaired or normal glucose tolerance. Orlistat shows efficacy in reducing cardiovascular risk factors irrespective of diabetic status or a confirmed diagnosis of metabolic syndrome. The benefit of orlistat in reducing the disease burden of obese patients with concomitant disorders has also been shown. Orlistat significantly delayed the progression to type 2 diabetes compared with placebo in obese patients with impaired glucose tolerance at baseline in the 4-year randomised, double-blind, multicentre XENDOS trial. Orlistat is generally as effective as sibutramine in producing weight loss; when the drugs are used in combination in obese patients with or without type 2 diabetes, weight loss is generally increased compared with orlistat alone. Orlistat and sibutramine are also generally equivalent with regard to improvements in diabetic parameters, but orlistat recipients had significant improvements in blood pressure compared with sibutramine recipients. Several well designed, fully published pharmacoeconomic studies analysing a range of perspectives, from the healthcare system to the patient, have shown that orlistat is a cost-effective treatment for obese adult patients with or without type 2 diabetes. Orlistat is generally well tolerated in adults and adolescents. Adverse effects experienced by orlistat recipients were generally mild and transient, with most resolving within a few weeks of treatment. The most common adverse events in recipients of orlistat are associated with the gastrointestinal tract. Tolerability profiles are similar in adults and adolescents, as well as in patients with type 2 diabetes or the metabolic syndrome.