Orlistat (Xenical and Alli): how the fat-blocker works

Key takeaways

• Orlistat blocks gut enzymes that digest fat, preventing about 30% of dietary fat from being absorbed at the 120 mg prescription dose.^[1]
• It is FDA approved as Xenical (120 mg, prescription, 1999) and Alli (60 mg, over the counter, 2007), always with a reduced-calorie, lower-fat diet.^[4]
• In the four-year XENDOS trial, weight loss was 5.17% vs 2.75% on placebo, and new diabetes was 5.5% vs 8.3%, mainly in people with impaired glucose tolerance.^[1]
• Oily spotting, gas with discharge and urgent bowel movements are common, especially after high-fat meals; a daily multivitamin is needed because fat-soluble vitamins can drop.^[1]
• Rare serious risks include liver injury and oxalate kidney damage, and orlistat interacts with cyclosporine, levothyroxine, warfarin, amiodarone, antiseizure and HIV medicines.^[1]

In short: Orlistat is a weight-loss medicine that works in the gut, not the brain: it blocks the enzymes that digest fat, so about 30% of the fat you eat passes out of the body unabsorbed. It comes in two FDA-approved strengths: Xenical (120 mg, prescription, approved in 1999) and Alli (60 mg, over the counter, approved in 2007). Both are taken with fat-containing meals alongside a reduced-calorie, lower-fat diet. The trade-off is digestive side effects such as oily spotting and urgent bowel movements, and the need for a daily multivitamin (checked on DailyMed and Drugs@FDA on 2026-10-06).

Orlistat is one of the oldest weight-loss medicines still on the market and one of the most studied, including a four-year trial. It produces smaller average weight loss than newer medicines, but it does not act on the brain, is not a controlled substance, and is available without a prescription at the lower strength. This page explains how it works, what the trials showed, the side effects and how to reduce them, the vitamin and medicine interactions, and what it costs. It is general education, not personal medical advice. Please research your options, talk with a licensed doctor or pharmacist and get evaluated before starting, especially if you take other medicines.

How orlistat works

The label describes orlistat as a reversible inhibitor of gastrointestinal lipases, the enzymes in the stomach and small intestine that break dietary fat (triglycerides) into pieces small enough to absorb. Orlistat binds to these enzymes inside the gut, so part of the fat in a meal passes through undigested. At the prescription dose of 120 mg three times a day, it blocks about 30% of dietary fat absorption, and the calories in that fat are not absorbed. Higher doses do not add benefit. The effect starts within 24 to 48 hours and wears off within 48 to 72 hours of stopping. The label notes that very little orlistat reaches the bloodstream; it works inside the gut rather than on appetite.

This mechanism explains both the benefit and the side effects: the unabsorbed fat has to leave the body, which causes oily stools, especially after a high-fat meal. It also explains why fat-soluble vitamins (A, D, E, K and beta-carotene) can drop, and why a multivitamin taken at a different time of day is part of the routine.

Two strengths: Xenical and Alli

	Xenical	Alli
Strength	120 mg capsule	60 mg capsule
Access	Prescription	Over the counter
FDA approval	April 23, 1999 (NDA 020766)	February 7, 2007 (NDA 021887)
Labeled for	Obesity management (weight loss and maintenance) and reducing regain after weight loss; BMI 30+, or 27+ with risk factors such as high blood pressure, diabetes or high cholesterol; studied in teens 12 to 16	Weight loss in overweight adults 18 and older, with a reduced-calorie, low-fat diet
How it is taken	One capsule with each main meal containing fat, up to three a day	One capsule with each meal containing fat, no more than three a day
Made by (label)	CHEPLAPHARM; distributed by H2-Pharma	Haleon

A generic orlistat 120 mg capsule is also on DailyMed. The rest of this page focuses on what the prescription label says; our Alli page covers the over-the-counter version and its Drug Facts label in detail.

Who it is labeled for, and who should not take it

Xenical is labeled for people with a BMI of 30 or more, or 27 or more with other risk factors, together with a reduced-calorie diet; safety and effectiveness below age 12 have not been established. The label says to rule out medical causes of weight gain, such as an underactive thyroid, before prescribing. Our BMI calculator can show where you stand, but only a clinician can decide whether orlistat fits you. Xenical should not be used:

• during pregnancy,
• by people with chronic malabsorption syndrome (problems absorbing food),
• by people with cholestasis (reduced bile flow), or
• by anyone allergic to orlistat or the capsule ingredients.

Extra care is needed for people with a history of kidney stones, high oxalate levels or kidney disease, and for people taking cyclosporine, levothyroxine, warfarin or other blood thinners, amiodarone, antiseizure medicines or HIV medicines (see interactions below). The label also notes the potential for misuse by people with anorexia or bulimia.

How it is taken, in general

Follow the instructions you are given; your clinician or pharmacist can help adjust timing around your other medicines. Our nutrition guide and calorie deficit guide can help you plan meals that fit the label’s diet advice.

What the trials showed

One year. In five pooled trials summarized in the label, people on Xenical lost 13.4 lb on average over a year, compared with 5.8 lb on placebo, both with a reduced-calorie diet; the average difference was about 3% of body weight. Depending on the trial, 35% to 55% of people on Xenical lost at least 5% of their weight, compared with 16% to 27% on placebo.

Four years (XENDOS). In 3,304 adults with obesity, average weight loss after four years was 5.17% on Xenical versus 2.75% on placebo, and 45% versus 28% still had at least 5% off their starting weight. The cumulative rate of new type 2 diabetes was 5.5% versus 8.3%, a 34% relative reduction; the benefit was concentrated in people who started with impaired glucose tolerance (18.7% vs 27.2%), and there was no reduction in those who started with normal glucose tolerance. Only 52% of the Xenical group and 34% of the placebo group completed the four years.

• Placebo
• Xenical

Average weight loss at 4 years2.75%5.17%

Still 5% or more below starting weight28%45%

New type 2 diabetes, all participants8.30%5.50%

New type 2 diabetes, impaired glucose tolerance at start27.20%18.70%

XENDOS: four years of orlistat 120 mg vs placebo

Item	Placebo	Xenical
Average weight loss at 4 years	2.75%	5.17%
Still 5% or more below starting weight	28%	45%
New type 2 diabetes, all participants	8.30%	5.50%
New type 2 diabetes, impaired glucose tolerance at start	27.20%	18.70%

3,304 adults with obesity. Diabetes rates are life-table rates adjusted for dropouts. For the diabetes rows, a shorter Xenical bar is better.

Source: Xenical prescribing information, section 14.4 and Table 10 (DailyMed) (checked on October 6, 2026)

Keeping weight off. Xenical is also labeled to reduce weight regain. In three studies of people who had already lost weight, those switched to placebo regained 52% to 63% of the lost weight over the next year, while those on Xenical regained 26% to 35%.

• Placebo
• Xenical

Study 14119C52%26%

Study 1418563%35%

Study 1430253%32%

Share of previously lost weight regained over one year

Item	Placebo	Xenical
Study 14119C	52%	26%
Study 14185	63%	35%
Study 14302	53%	32%

Participants had lost weight on diet alone (14302) or after a year of Xenical (14119C, 14185). Shorter bars mean less regain.

Source: Xenical prescribing information, section 14.2 (DailyMed) (checked on October 6, 2026)

Other measures and populations. After one year, total and LDL cholesterol and blood pressure improved slightly more than on placebo. In adults with type 2 diabetes on sulfonylureas, 30% versus 13% lost at least 5% of their weight, and more could lower their diabetes medicine. In 539 adolescents aged 12 to 16, BMI fell by 0.55 on average versus a 0.31 rise on placebo. A two-year European trial that compared both strengths found first-year weight loss of 9.7% on 120 mg, 8.6% on 60 mg and 6.6% on placebo, alongside diet. The American Gastroenterological Association’s 2022 guideline suggested against using orlistat for weight management, while suggesting several other medicines; as always, the choice is between you and your clinician.

Side effects

The digestive side effects are a direct result of how orlistat works. They usually start within the first three months; about half of episodes last less than a week and most no more than four weeks, though some people have them for six months or longer. They become less common in the second year and are worse after high-fat meals.

• Placebo
• Xenical 120 mg

Oily spotting1.3%26.6%

Gas with discharge1.4%23.9%

Urgent need to have a bowel movement6.7%22.1%

Fatty or oily stool2.9%20%

Oily evacuation0.8%11.9%

More frequent bowel movements4.1%10.8%

Fecal incontinence0.9%7.7%

Digestive side effects in the first year

Item	Placebo	Xenical 120 mg
Oily spotting	1.3%	26.6%
Gas with discharge	1.4%	23.9%
Urgent need to have a bowel movement	6.7%	22.1%
Fatty or oily stool	2.9%	20%
Oily evacuation	0.8%	11.9%
More frequent bowel movements	4.1%	10.8%
Fecal incontinence	0.9%	7.7%

Seven placebo-controlled trials: 1,913 people on Xenical and 1,466 on placebo in year 1. Oily discharge may be clear, orange or brown.

Source: Xenical prescribing information, Table 2 (DailyMed) (checked on October 6, 2026)

In controlled trials, 8.8% of people on Xenical stopped because of side effects, compared with 5.0% on placebo, mostly for digestive reasons. Other side effects reported slightly more often than on placebo include abdominal discomfort, rectal discomfort, headache, back pain, menstrual irregularity, anxiety and fatigue. Eating less fat at each meal is the main way to reduce digestive symptoms. Our weight-loss pills guide compares how tolerable different pills tend to be.

Vitamins

Because orlistat blocks fat absorption, it can lower fat-soluble vitamins. In trials of people who did not take supplements, low vitamin levels on two or more visits were more common on Xenical, especially vitamin D and vitamin E. In a teen trial where everyone took a multivitamin, low levels were rare in both groups. This is why the label tells everyone to take a daily multivitamin with vitamins A, D, E, K and beta-carotene, spaced at least 2 hours from orlistat.

• Placebo
• Xenical

Vitamin D6.6%12%

Beta-carotene1.7%6.1%

Vitamin E1%5.8%

Vitamin A1%2.2%

Low vitamin levels on two or more visits, adults not taking supplements

Item	Placebo	Xenical
Vitamin D	6.6%	12%
Beta-carotene	1.7%	6.1%
Vitamin E	1%	5.8%
Vitamin A	1%	2.2%

First and second year of treatment, adults with normal levels at the start who were not given vitamins.

Source: Xenical prescribing information, Table 4 (DailyMed) (checked on October 6, 2026)

Serious risks

• Liver injury: rare reports of severe liver injury, including liver failure, some leading to transplant or death.
• Kidney problems: higher urinary oxalate, oxalate kidney stones and oxalate nephropathy with kidney failure have been reported; kidney function should be monitored in people at risk.
• Gallstones: substantial weight loss raises the risk; in XENDOS, gallstones were reported in 2.9% on Xenical versus 1.8% on placebo.
• Other rare reports: serious allergic reactions, pancreatitis (no causal link established) and lower digestive bleeding (mostly not serious).

Interactions

• Cyclosporine: levels drop; take it 3 hours after orlistat, with extra monitoring.
• Levothyroxine: hypothyroidism has been reported; take the two at least 4 hours apart and monitor thyroid function.
• Warfarin and other blood thinners: lower vitamin K absorption can change clotting tests; close monitoring is needed.
• Amiodarone: lower exposure and possibly reduced effect.
• Antiseizure medicines: convulsions have been reported; watch for changes in seizure frequency.
• HIV medicines: loss of viral control has been reported; HIV RNA levels should be monitored often.
• Diabetes medicines: doses may need lowering as weight falls.

Common misunderstandings

• “It lets me eat whatever I want.” The opposite: the label tells people to follow a reduced-calorie diet with about 30% of calories from fat, and warns that digestive side effects increase with high-fat meals.
• “It burns fat.” Orlistat does not burn body fat or raise metabolism; it stops some dietary fat from being absorbed, and the label credits the resulting calorie deficit.
• “More capsules work better.” The label says doses above 120 mg three times a day have not shown extra benefit, and Alli says not to take more than 3 capsules a day.
• “The vitamins are optional.” Low vitamin D, E and beta-carotene were clearly more common in people who did not take supplements, so the daily multivitamin is part of the treatment.
• “It is just a supplement.” Orlistat is an FDA-approved drug with real interactions; check with a pharmacist before combining it with other medicines.

Pregnancy and breastfeeding

Xenical is contraindicated in pregnancy, because weight loss offers no benefit during pregnancy and may harm the fetus. It is not known whether it passes into breast milk, and the label advises caution; the Alli Drug Facts label says not to use it while pregnant or breastfeeding. Talk with your clinician about pregnancy plans.

Cost and insurance

Neither the Xenical distributor nor the Alli maker publishes a consumer price we could verify. As a neutral benchmark, Medicaid’s NADAC shows what pharmacies pay on average. At the full prescription dose of three capsules a day, a 30-day supply (90 capsules) works out as shown below. Interestingly, the brand cost pharmacies less than the generic in the September 2026 data. Your price will be higher and depends on your pharmacy and plan.

Generic orlistat 120 mg$629.90

Xenical 120 mg (brand)$413.81

What pharmacies pay for 90 capsules of orlistat 120 mg (NADAC)

Item	Value
Generic orlistat 120 mg	$629.90
Xenical 120 mg (brand)	$413.81

NADAC per capsule multiplied by 90 (three a day for 30 days). Pharmacy acquisition cost, not a retail price.

Source: CMS data.medicaid.gov, NADAC 2026 (rates effective 2026-09-23), InstaTuck calculation (checked on October 6, 2026)

Medicare is prohibited by law from covering drugs used specifically for weight loss, and commercial coverage varies. Alli is sold over the counter without insurance. Our insurance guide and costs hub explain what is usually covered.

Alternatives to discuss with your clinician

Medicines with larger average weight loss in their own trials include the combination pills Qsymia and Contrave and the GLP-1 family, such as the Wegovy pill, Foundayo and weekly Wegovy. Short-term phentermine is another older option. Each has its own side effects, costs and rules, listed on the medications hub. Whatever you choose, the basics in how to lose weight and keeping weight off matter most over time.

FDA status and approved uses

Indication	Labeled population	For weight	Approved	Source
Obesity management including weight loss and weight maintenance with a reduced-calorie diet; reduce the risk for weight regain after prior weight loss (Xenical 120 mg)	Patients with an initial BMI of 30 kg/m2 or more, or 27 kg/m2 or more with other risk factors (e.g., hypertension, diabetes, dyslipidemia)	Yes	April 23, 1999	Source
Weight loss aid, with a reduced-calorie, low-fat diet (Alli 60 mg, OTC)	Overweight adults 18 years and older	Yes	February 7, 2007	Source

From the FDA label. Who a medicine is labeled for is not the same as whether it fits you; only a clinician can decide that.

How it is taken (in general)

Xenical: one 120 mg capsule with each main meal containing fat (during or up to 1 hour after), up to three times a day; skip if a meal has no fat. Reduced-calorie diet with about 30% of calories from fat spread over three meals. Daily multivitamin with A, D, E, K and beta-carotene at least 2 hours apart (e.g., bedtime). Cyclosporine 3 hours after; levothyroxine 4 hours apart. Follow your prescriber.

This is what the label describes in general, never a personal dose or schedule. Follow your prescriber.

What studies showed

Trial	Population	Duration	Outcome as reported
Pooled one-year trials	Five multicenter placebo-controlled trials in adults with obesity	1 year	Mean weight loss 13.4 lb vs 5.8 lb with placebo; 35.5% to 54.8% vs 16.0% to 27.4% lost 5% or more.[1]
XENDOS	3,304 adults with obesity, normal or impaired glucose tolerance	4 years	Weight -5.17% vs -2.75%; cumulative diabetes incidence 5.5% vs 8.3% (34% relative reduction), driven by people with impaired glucose tolerance.[1]
European Orlistat Obesity Study	Adults with BMI 28 to 43; orlistat 60 mg, 120 mg or placebo	2 years	Year-1 weight loss 9.7% (120 mg), 8.6% (60 mg), 6.6% (placebo); less regain in year 2.[6]

Average results from trials; individual results vary. Results from different trials cannot be compared directly.

Side effects

Common side effect	How often (label)
Oily spotting	26.6% vs 1.3% placebo (year 1)
Flatus with discharge	23.9% vs 1.4% placebo
Fecal urgency	22.1% vs 6.7% placebo
Fatty or oily stool	20.0% vs 2.9% placebo
Oily evacuation	11.9% vs 0.8% placebo
Increased defecation	10.8% vs 4.1% placebo
Fecal incontinence	7.7% vs 0.9% placebo

Serious risks

• Severe liver injury (rare), including hepatic failure
• Oxalate nephrolithiasis and oxalate nephropathy with renal failure
• Cholelithiasis
• Decreased absorption of fat-soluble vitamins and beta-carotene
• Drug interactions (cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptics, antiretrovirals)

Warnings and who should not use it

Who should not use it (per the label)

• Pregnancy
• Chronic malabsorption syndrome
• Cholestasis
• Known hypersensitivity to orlistat or any component

Interactions, pregnancy and breastfeeding

Drug or class	What the label says
Cyclosporine	Reduced cyclosporine levels; give cyclosporine 3 hours after orlistat and monitor.
Levothyroxine	Hypothyroidism reported; separate by at least 4 hours and monitor thyroid function.
Warfarin and other anticoagulants	Lower vitamin K absorption; monitor coagulation closely.
Amiodarone	Reduced exposure; possible reduced effect.
Antiepileptic drugs	Convulsions reported; monitor seizure frequency.
Antiretroviral drugs	Loss of virological control reported; monitor HIV RNA.
Fat-soluble vitamin supplements	Absorption reduced; take the multivitamin at least 2 hours apart.

Pregnancy and breastfeeding

Xenical is contraindicated in pregnancy (weight loss offers no benefit and may cause fetal harm). Not known whether it is present in human milk; use caution. The Alli Drug Facts label says not to use if pregnant or breastfeeding.

Cost, insurance and savings

Price	Amount	Basis	Checked on
Other	629.90 USD	NADAC pharmacy acquisition cost, 90 generic orlistat 120 mg capsules (rate effective 2026-09-23)	October 6, 2026
Other	413.81 USD	NADAC pharmacy acquisition cost, 90 Xenical 120 mg capsules (rate effective 2026-09-23)	October 6, 2026

Prices change often and depend on pharmacy, plan and location. Insurance can change what you pay. Every price shows the date we checked it.

Questions to ask your doctor or pharmacist

• Is orlistat a good fit for my health and goals, or would another medicine suit me better?
• Do any of my medicines, such as levothyroxine, warfarin, cyclosporine or antiseizure drugs, need timing changes or monitoring?
• Which multivitamin should I take, and when?
• Should I use prescription Xenical or over-the-counter Alli?
• Do I have any history of kidney stones, gallbladder or liver problems that changes the risks?

Frequently asked questions

How does orlistat work?

It blocks lipases, the enzymes in the stomach and small intestine that digest fat. At 120 mg three times a day, about 30% of the fat you eat is not absorbed and leaves the body in the stool.

What is the difference between Xenical and Alli?

Both contain orlistat. Xenical is a 120 mg prescription capsule; Alli is a 60 mg over-the-counter capsule for overweight adults 18 and older. Both are taken with fat-containing meals, up to three times a day.

How much weight can you lose with orlistat?

In one-year trials, people on Xenical lost 13.4 lb on average vs 5.8 lb on placebo, both with diet. In the four-year XENDOS trial, average loss was 5.17% vs 2.75%.

How can I reduce the oily side effects?

The label explains that side effects increase with high-fat meals. Following a diet with about 30% of calories from fat, spread across meals, reduces them. Talk with your clinician or pharmacist if they persist.

Why do I need a multivitamin with orlistat?

Orlistat reduces absorption of fat-soluble vitamins A, D, E, K and beta-carotene. The label says to take a daily multivitamin containing them at least 2 hours before or after orlistat, for example at bedtime.

Can I take orlistat with thyroid medicine?

Hypothyroidism has been reported when the two are combined. The label says to take levothyroxine and orlistat at least 4 hours apart and to monitor thyroid function.

Is orlistat safe for the liver and kidneys?

Rare cases of severe liver injury and of oxalate kidney stones and kidney damage have been reported. Stop and contact a clinician if you notice signs of liver or kidney problems.

Does orlistat prevent diabetes?

In XENDOS, new type 2 diabetes was less common on Xenical (5.5% vs 8.3%) over four years, with the benefit seen in people who started with impaired glucose tolerance; it is not approved as a diabetes-prevention medicine.

Can teenagers take orlistat?

Xenical was studied in adolescents aged 12 to 16, and safety below 12 has not been established. Alli is only for adults 18 and older. A pediatric clinician should guide any decision.

Official sources

• Prescribing information (FDA label)
• FDA approval letter or page

References

1. XENICAL (orlistat) capsules: prescribing information. H2-Pharma / CHEPLAPHARM, via DailyMed, 2026. (accessed October 6, 2026) Drug label
2. Orlistat capsules 120 mg: prescribing information. H2-Pharma, via DailyMed. (accessed October 6, 2026) Drug label
3. ALLI (orlistat 60 mg) capsules: Drug Facts. Haleon, via DailyMed, 2026. (accessed October 6, 2026) Drug label
4. Drugs@FDA: Xenical, NDA 020766 (original approval 1999-04-23). U.S. Food and Drug Administration. (accessed October 6, 2026) Government page
5. Drugs@FDA: Alli, NDA 021887 (original approval 2007-02-07). U.S. Food and Drug Administration. (accessed October 6, 2026) Government page
6. Rossner S, Sjostrom L, Noack R, Meinders AE, Noseda G. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obesity Research, 2000. doi:10.1038/oby.2000.8 · PMID 10678259 (accessed October 6, 2026) Randomized trial
7. Grunvald E, Shah R, Hernaez R, et al.. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology, 2022. doi:10.1053/j.gastro.2022.08.045 · PMID 36273831 (accessed October 6, 2026) Guideline
8. FDA Approves Labeling Changes for OTC Weight Loss Drug alli (Orlistat) to Warn of Risk of Kidney Stones and Kidney Injury. U.S. Food and Drug Administration. (accessed October 6, 2026) Government page
9. NADAC (National Average Drug Acquisition Cost) 2026. Centers for Medicare and Medicaid Services (data.medicaid.gov). (accessed October 6, 2026) Government page
10. A New Use for Wegovy Opens the Door to Medicare Coverage for Millions of People with Obesity. KFF, 2024. (accessed October 6, 2026) Other

Facts checked on October 6, 2026

Educational information, not medical advice. Talk with a qualified healthcare professional about your own situation. In an emergency call 911.