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.