FDA approved orlistat in 1999 as a prescription weight drug that blocks fat absorption
Orlistat, approved in 1999 as Xenical, works by blocking fat absorption in the gut, and later became available over the counter at half the dose as Alli.
The FDA approved orlistat, sold under the brand name Xenical, in 1999 as a prescription weight-loss drug for adults with a body mass index (BMI) of 30 or higher, or 27 or higher with weight-related risk factors such as high blood pressure or diabetes [1][2]. The 120-milligram prescription version is also approved for adolescents 12 and older [1].
Orlistat works in the digestive tract rather than by changing appetite. It blocks lipase, an enzyme in the digestive tract that breaks dietary fat into smaller parts so the body can use or store it for energy [2]. When the drug is taken with a meal, about 25 percent of the fat in that meal is not broken down and passes out of the body in bowel movements [2].
Xenical is taken as a 120-mg capsule three times a day before fat-containing meals [1]. A lower-dose version became available without a prescription in 2007: Alli, which contains 60 mg of orlistat per capsule [1]. Studies show the 60-mg dose is about 85 percent as effective as the 120-mg dose [1]. Alli is approved for adults 18 and older with a BMI of 25 or higher, while the prescription version's approved BMI ranges are narrower [2].
Weight loss with orlistat has been described as modest. In some studies, more than 40 percent of people taking Alli while following a calorie-restricted diet and increasing physical activity lost 5 percent or more of their body weight within a year, a threshold generally considered clinically meaningful because it can begin to lower the risk of heart disease and diabetes [2]. People who dieted, exercised and took Alli lost an average of 5.7 pounds (2.6 kilograms) more in one year than people who only dieted and exercised [2].
Side effects are mostly digestive and tied to undigested fat: oily discharge from the anus, oily stools, gas with oily discharge, more frequent bowel movements, urgent or hard-to-control bowel movements, and stomach pain or upset stomach [2]. They generally lessen over time and with proper use of the drug [2]. Orlistat can reduce absorption of fat-soluble nutrients, including beta carotene and vitamins A, D, E and K, so the label advises taking a multivitamin at least two hours after the last dose of the day [2]. Fat intake is recommended to stay at no more than 30 percent of total calories, with the manufacturer suggesting about 15 grams of fat per meal; a high-fat meal makes digestive side effects more severe [2].
In 2010, the FDA published a safety review of orlistat after rare reports of serious liver injury in people using it. The agency found no evidence confirming that orlistat caused the reported injuries, but the Alli and Xenical labels were revised to list warning signs to watch for, including itching, loss of appetite, yellow eyes or skin, light-colored stool and brown urine [2].
Why it matters for patients
Orlistat's effects come from the gut, so it does not require an injection, and the 60-mg version can be bought over the counter by adults 18 and older with a BMI of 25 or higher [1][2]. The prescription 120-mg version is an option for adults with a BMI of 30 or higher, or 27 or higher alongside conditions such as high blood pressure or diabetes, and for adolescents 12 and older [1][2].
The weight loss reported with orlistat is modest, and the digestive side effects are common and tied to the fat in meals [2]. The label's advice on timing a multivitamin at least two hours after the last dose reflects the drug's effect on vitamins A, D, E and K [2]. Mayo Clinic guidance says that if a person has not lost 5 percent of body weight within a year on diet, exercise and the drug, stopping may be a reasonable choice [2]. Head-to-head studies of orlistat against GLP-1 weight-loss drugs such as semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound) have not been reported, so how the options compare has not been established.
What happened next
Sources
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