- 102 Downloads
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 120mg dose of orlistat 3 times daily (with each main meal) is optimal.
Controlled studies have established that orlistat 120mg 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 120mg 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.
KeywordsAdis International Limited Placebo Recipient Orlistat Sibutramine Hypocaloric Diet
Unable to display preview. Download preview PDF.
- 12.Roche Laboratories. Xenical® (orlistat) Product information. Nutley (NJ), 1999Google Scholar
- 13.Guerciolini R. Mode of action of orlistat. Int J Obes 1997; 21 Suppl. 3:S12–23Google Scholar
- 32.Finer N, James WP, Kopelman PG, et al. One-year treatment of obesity: a randomised, double-blind, placebo-controlled, multicentre study of orlistat (Xenical®), a gastrointestinal lipase inhibitor. Int J Obes (In press)Google Scholar
- 33.Noack R. Two-year study of orlistat in the treatment of obesity [abstract]. 79th Annual Meeting of the American Endocrine Society: 1997 Jun 11–14; MinneapolisGoogle Scholar
- 34.Hauptman J, Lucas C, Boldrin M, et al. Orlistat, a gastrointestinal lipase inhibitor, in the long-term treatment of obesity in a primary care setting. Arch Fam Med (In press)Google Scholar
- 35.Drent ML, Larsson I, William-Olsson T, et al. Orlistat (RO 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Int J Obes 1995 Apr; 19: 221–6Google Scholar
- 36.Drent ML, van der Veen EA. Lipase inhibition: a novel concept in the treatment of obesity. Int J Obes 1993; 17: 241–4Google Scholar
- 37.Rössner S, Sjöström L, Noack R, et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res (In press)Google Scholar
- 39.Stolshek B, Mathias S, Pasta D, et al. Health-related quality of life (HRQoL) during treatment with orlistat (Xenical®) [abstract no. 518]. Int J Obes 1999 May; 23 Suppl. 5: S158Google Scholar
- 42.Rissanen A. Orlistat-induced weight loss improves response to oral glucose tolerance testing [abstract no. P677]. Int J Obes 1998 Aug; 22 Suppl. 3: S274Google Scholar
- 43.Watkins PJ, Joint Working Party of the British Diabetic Association, the Research Unit of the Royal College of Physicians, and the Royal College of General Practitioners. Guidelines for good practice in the diagnosis and treatment of non-insulin-dependent diabetes mellitus. J R Coll Physicians Lond 1993 Jul; 27(3): 259–66Google Scholar
- 44.Pataky Z, Golay A. Effect of treatment with orlistat for one-year on blood pressure in obese patients [abstract no. 582]. Int J Obes 1999; 23 Suppl. 5: S175Google Scholar
- 45.Lucas C, Hauptman J, Boldrin M, et al. Effect of orlistat on weight loss and cardiovascular disease risk factors in obese hypertensive patients. Hoffman-La Roche, Nutley (NJ), 1999. (Data on file)Google Scholar
- 46.Canovatchel W. Long-term tolerability profile of orlistat, an intestinal lipase inhibitor [abstract no. 769]. Diabetologia 1997 Jun; 40 Suppl. 1: A196Google Scholar
- 47.Roche Laboratories. Expert report on additional breast cancer information for Xenical® (orlistat). Roche Laboratories (New Jersey). 1999, (Data on file)Google Scholar
- 48.Roche Products Ltd. Xenical® (orlistat) Product information. Hertfordshire, UK, 1998Google Scholar
- 55.Pi-Sunyer X. Guidelines for the approval and use of drugs to treat obesity — a position paper of the North American Association for the Study of Obesity. Obes Res 1995 Sep; 3: 473–8Google Scholar
- 59.Goldenberg MM, Caspi A. Orlistat: a novel concept in the treatment of obesity. PT 1998 Nov; 23: 571–80Google Scholar
- 61.Jones SP, Smith IG, Kelly F, et al. Long-term weight loss with sibutramine [abstract]. Int J Obes 1995; 19 Suppl. 2: 41Google Scholar
- 62.Knoll Pharmaceutical Company. Meridia® (sibutramine hydrochloride monohydrate) Product information. Mount Olive (NJ), 1997Google Scholar