Orlistat
A capsule that blocks part of the fat you eat from being absorbed. It works in the gut, not in the brain. Xenical is the prescription brand.
Orlistat (known as Xenical, Alli)
Also searched as: Xenical, Alli, orlistat capsules.
Educational information. This page does not give dosing instructions or tell you what to take. Ask a prescriber about your own care.
In plain English
Orlistat works differently from the other weight-loss drugs. It blocks lipase, an enzyme that breaks down dietary fat, so roughly a third of the fat you eat passes through undigested. It is not absorbed into the body in any large amount, and it does not affect appetite.
The effect is modest. In a 4-year trial of 3,305 adults (XENDOS), people on orlistat lost about 5.8 kg on average, versus 3.0 kg on placebo, and fewer developed type 2 diabetes (6.2% vs 9.0%). About half of the people on orlistat finished the trial.
The side effects follow directly from the mechanism: oily spotting, urgent bowel movements and loose or fatty stools, mostly in the first three months and worse after high-fat meals. Xenical is the prescription capsule. A lower-strength over-the-counter capsule is sold as Alli, which was not separately checked here.
Brand names and products
A generic name identifies the drug itself. A brand name identifies one company's product. One drug can come in several products with different forms and approved uses, so the brand name often tells you more about what a prescription is for.
Sold in the U.S. as Xenical. A separate page for this brand has not been added to the atlas yet. The forms table below lists its approved use.
Approved and investigational. Orlistat 120 mg (Xenical) is FDA-approved for weight management. The lower-strength over-the-counter version has its own label, which was not reviewed here.
How it works
Orlistat inhibits gastric and pancreatic lipases, the enzymes that split dietary fat so it can be absorbed. The undigested fat leaves the body in stool. Because less fat is absorbed, so are some fat-soluble vitamins, which is why the label advises a daily multivitamin.
Forms and approval status
| Form | How it is taken | U.S. status |
|---|---|---|
| Orlistat 120 mg capsules (Xenical) | With meals, up to three times a day. Taken with meals that contain fat. A daily multivitamin is advised by the label. Follow the label and your prescriber. | Approved in the U.S. for weight loss and weight maintenance with a reduced-calorie diet, and to reduce regain after weight loss, in adults with a BMI of 30 or more, or 27 or more with risk factors. Studied in adolescents 12 to 16. A lower-strength over-the-counter version (Alli) is sold separately. |
What the trials found
These are group averages from published trials in adults without diabetes unless stated. See how to read trial numbers before comparing.
XENDOS
Average change in body weight, in kilograms. Every bar uses one scale, 0 to 10 kilograms.
- People studied
- 3,305 adults with a body mass index of 30 or higher; 79% had normal blood sugar handling and 21% had impaired glucose tolerance
- Length
- 208 weeks (4 years)
- Compared with
- Placebo, with lifestyle changes in both groups
- What was measured
- Average weight loss after 4 years, as reported
- Analysis approach
- Intention to treat. A second analysis that carried baseline weight forward for people who dropped out gave 3.6 kg with orlistat vs 1.4 kg with placebo.
- Other results
- Type 2 diabetes appeared in 6.2% of people on orlistat vs 9.0% on placebo over 4 years. The difference was found only in the impaired glucose tolerance subgroup.
- Safety
- Side effects are not summarized in the study abstract. See the official label linked on the orlistat page.
- Limits
- Funded by the manufacturer. Only 52% of the orlistat group and 34% of the placebo group finished treatment. Group averages do not predict one person's result.
Sources: Torgerson JS 2004
Safety
Based on the FDA-approved label for Xenical. The official label is the controlling source for warnings. The points below are a summary and may be incomplete.
Boxed warning and label notes
- Orlistat 120 mg capsules (Xenical): No boxed warning. Contraindicated in pregnancy, chronic malabsorption and cholestasis.
Warnings labels describe
- Rare reports of severe liver injury, including liver failure and death, after the drug reached the market.
- Can cause oxalate kidney stones and kidney damage in higher-risk people. The label says to stop it if oxalate nephropathy develops.
- Can lower absorption of fat-soluble vitamins and beta-carotene, and can interact with cyclosporine, levothyroxine, warfarin and some anti-seizure and HIV drugs.
- Substantial weight loss from any cause raises gallstone risk. Not for use in pregnancy or in people with chronic malabsorption or cholestasis.
Most common in trials
- Oily spotting
- Gas with oily discharge
- Urgent bowel movements
- Fatty or oily stools
- Increased bowel movements
- Fecal incontinence
Less common but serious
- Severe liver injury (rare)
- Oxalate kidney stones or kidney failure
- Gallstones
- Lower absorption of fat-soluble vitamins
What is still unknown
- How its modest average benefit compares with the newer medicines. No head-to-head trial is recorded in this atlas.
- How much weight people keep off after stopping.
- Long-term safety beyond the 4-year XENDOS trial.
Compiled from public information: FDA-approved labels, manufacturer websites, ClinicalTrials.gov and published journal articles. Sources are listed at the bottom of this page.
Sources
- Xenical (orlistat) capsules: prescribing information H2-Pharma LLC, on DailyMed (U.S. National Library of Medicine). FDA-approved label revised 7/2024. Official FDA label on DailyMed
- XENical in the prevention of diabetes in obese subjects (XENDOS) study Torgerson JS, et al. Diabetes Care. 2004;27(1):155-161. PMID 14693982. Funding: Roche. Journal article
- DailyMed: current FDA drug labels U.S. National Library of Medicine. Regulator