Pharmacotherapy for Obesity

A Field in Crisis?

Wiebke Fenske; Jennifer Parker; Stephen R Bloom

Disclosures

Expert Rev Endocrinol Metab. 2011;6(4):563-577. 

In This Article

Peripherally Acting Agents Reducing the Efficiency of Digestion

Orlistat

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),[204] 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.

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