Peripherally Acting Agents Reducing the Efficiency of Digestion
Orlistat (Xenical®; Roche) is the only anti-obesity drug that remains on the market after the withdrawal of sibutramine in 2010. This stable analog of lipstatin, a naturally occurring lipase inhibitor produced by Streptomyces toxytricini, is indicated for the treatment of obesity in conjunction with a reduced-calorie diet. Orlistat acts locally to potently inhibit pancreatic and gastric lipase and thus the hydrolysis of triglycerides. As a result, only approximately two-thirds of dietary triglyceride intake is absorbed by the small intestine. Orlistat has been shown to be modestly efficacious (120 mg three-times daily) in several long-term randomized clinical trials where it induced weight loss of approximately 2–4 kg more than diet and exercise alone.[5–7] The most common side effects are diarrhea, flatulence, bloating, abdominal pain and dyspepsia. After independent reports of liver injuries (including six cases of liver failure between 1999 and 2008), the FDA has recently approved a label revision for orlistat containing an additional a warning of possible severe liver injury. Compounds that inhibit glucosidase (acarbose and miglitol) and thus the digestion of starches, which induces carbohydrate absorption, have little effect on weight.
Expert Rev Endocrinol Metab. 2011;6(4):563-577. © 2011 Expert Reviews Ltd.
Cite this: Pharmacotherapy for Obesity - Medscape - Jul 01, 2011.