Orlistat is the weight-loss drug that works in the gut instead of the brain, and the only one sold in the US without a prescription. It stops about a third of the fat in a meal from being absorbed. One of its trials ran four years, and the record shows a steady but modest effect: about 3% of body weight more than placebo after a year. The price paid for that is digestive, and the label is specific about it.
This page reads the US labels for Xenical (orlistat 120 mg, H2-Pharma, effective 9 January 2026) and Alli (orlistat 60 mg, Haleon, effective 18 March 2026), read on 3 November 2026, with the XENDOS trial and current pharmacy costs. It sets the GLP-1 figures this site already reports beside them, each with its population, and does not rank them. The other non-GLP-1 options are on GLP-1 alternatives.
How it works
Orlistat is a reversible inhibitor of gastrointestinal lipases, the enzymes that break down dietary fat. Undigested fat cannot be absorbed and leaves in the stool. Xenical's label states that at its labelled 120 mg three-times-daily schedule, orlistat inhibits dietary fat absorption by approximately 30%, and that alcohol does not change that. It does not act on appetite. That is the opposite of the GLP-1 class, which works mainly by reducing hunger; the mechanism is explained on how GLP-1 drugs work.
Xenical and Alli, side by side
| Xenical | Alli | |
|---|---|---|
| Strength | 120 mg capsule | 60 mg capsule |
| Status | Prescription | Over the counter |
| FDA approval | 23 April 1999 (NDA 020766) | 7 February 2007 (NDA 021887) |
| Who the label covers | Obesity management (BMI ≥30, or ≥27 with risk factors such as hypertension, diabetes or dyslipidaemia), and reducing regain after weight loss | Overweight adults 18 and older, with a reduced-calorie, low-fat diet |
| Labelled schedule | One capsule with each main meal containing fat, three times a day | per the Drug Facts panel |
| Evidence on the label | Seven 1–2-year trials and the 4-year XENDOS trial | Summary: 2–3 extra pounds for every 5 lost by diet; most lost 5–10 lb over 6 months |
Sources: Xenical label sections 1, 2 and 14; Alli Drug Facts; Drugs@FDA. The schedules are the labels' own statements, reported here, not instructions.
Both labels pair orlistat with a multivitamin containing fat-soluble vitamins, because orlistat also reduces their absorption. Xenical's label says the vitamin should be separated from orlistat by at least two hours, for example at bedtime, and that levothyroxine and orlistat should be at least 4 hours apart; Alli's says a multivitamin once a day at bedtime.
It is the only obesity drug on general sale in pharmacies. Whether a GLP-1 can be bought without a prescription — it cannot — is covered on is there an over-the-counter GLP-1?.
What the trials measured
One year. Pooled across five Xenical trials, mean weight loss in the intention-to-treat population was 13.4 lb on Xenical and 5.8 lb on placebo; the label puts the difference at about 3% of body weight. Of those who completed the year, 57% on Xenical and 31% on placebo lost at least 5%.
| Trial (label Table 6) | Lost ≥5%: Xenical | Placebo | Lost ≥10%: Xenical | Placebo |
|---|---|---|---|---|
| 14119B | 35.5% | 21.3% | 16.4% | 6.5% |
| 14119C | 54.8% | 27.4% | 24.8% | 8.2% |
| 14149 | 50.6% | 26.3% | 22.8% | 11.9% |
| 14161 (primary care) | 37.1% | 16.0% | 19.5% | 3.8% |
| 14185 | 42.6% | 22.4% | 17.7% | 9.9% |
The lowest figures come from the one trial run by primary-care doctors (14161) rather than obesity specialists, a reminder that the setting affects results.
Four years — XENDOS. 3,304 adults with obesity (55% women; age 30–58) were randomised to Xenical or placebo, both with lifestyle advice:
| Measure (XENDOS, label section 14.4) | Xenical | Placebo |
|---|---|---|
| Completed 4 years | 52% | 34% |
| Mean weight change at 4 years | −5.17% | −2.75% |
| Lost ≥5% at 4 years | 45% | 28% |
| Lost ≥10% at 4 years | 21% | 10% |
| Cumulative type 2 diabetes at 4 years | 5.5% | 8.3% |
One detail worth knowing: the trial's own publication reports the diabetes figures as 6.2% vs 9.0% (a 37.3% risk reduction), while the current label prints 5.5% vs 8.3% for the same trial (Torgerson et al., Diabetes Care 2004). The two sources do not explain the difference; it may reflect different analyses. Both show a reduction, and the paper's exploratory analysis attributes it to the 21% of participants who started with impaired glucose tolerance. Fewer than half of the placebo arm finished — a heavy dropout that weakens any four-year estimate.
Beside the GLP-1 figures
No trial compares orlistat with a GLP-1 medicine. These are separate trials with their populations:
| Medicine (trial) | Population | Length | Medicine | Placebo |
|---|---|---|---|---|
| Xenical (5 pooled trials) | Adults with obesity, most with risk factors | 1 year | about 3 points more than placebo (13.4 lb vs 5.8 lb) | — |
| Xenical (XENDOS) | Adults with obesity, normal or impaired glucose tolerance | 4 years | −5.17% | −2.75% |
| Semaglutide 2.4 mg (STEP 1) | Obesity or overweight with a related condition, no diabetes | 68 weeks | −14.9% | −2.4% |
| Tirzepatide 15 mg (SURMOUNT-1) | Obesity or overweight with a related condition, no diabetes | 72 weeks | −20.9% | −3.1% |
| Contrave (COR-I) | Obesity or overweight with a related condition | 56 weeks | −5.4% | −1.3% |
Sources: Xenical label; STEP 1; SURMOUNT-1; Contrave label. Orlistat's trials ran in the 1990s and 2000s with different diet programmes and dropout methods. Contrave's full record is on Contrave.
Side effects, from the label
Orlistat's side effects follow from its mechanism: the fat it blocks has to go somewhere.
| Adverse event (label Table 2) | Xenical, year 1 (N=1,913) | Placebo, year 1 (N=1,466) | Xenical, year 2 (N=613) | Placebo, year 2 (N=524) |
|---|---|---|---|---|
| Oily spotting | 26.6% | 1.3% | 4.4% | 0.2% |
| Flatus with discharge | 23.9% | 1.4% | 2.1% | 0.2% |
| Fecal urgency | 22.1% | 6.7% | 2.8% | 1.7% |
| Fatty/oily stool | 20.0% | 2.9% | 5.5% | 0.6% |
| Oily evacuation | 11.9% | 0.8% | 2.3% | 0.2% |
| Increased defecation | 10.8% | 4.1% | 2.6% | 0.8% |
| Fecal incontinence | 7.7% | 0.9% | 1.8% | 0.2% |
The label says these events usually first appear within 3 months, that about half of episodes last under a week and most no more than four weeks, and that they increase when more than 30% of daily calories come from fat. In the trials, 8.8% on Xenical and 5.0% on placebo stopped because of adverse events. The year-two rates are much lower, which partly reflects who stayed on the drug.
Other warnings on the label: reduced absorption of vitamins A, D, E and K; drug interactions with cyclosporine, levothyroxine, warfarin, amiodarone, anti-seizure drugs and HIV medicines; rare severe liver injury; oxalate kidney stones and kidney injury; gallstones with substantial weight loss. Contraindicated in pregnancy, chronic malabsorption, cholestasis and known allergy. Alli's panel tells people with an organ transplant, or taking cyclosporine, not to use it. The GLP-1 class's digestive side effects, mostly nausea and constipation rather than oily stool, are on GLP-1 side effects.
What it costs
The National Average Drug Acquisition Cost survey (NADAC, Centers for Medicare & Medicaid Services) records what US pharmacies pay. For the week of 21 October 2026:
| Product | Pharmacy cost per capsule | 90 capsules (a month at the labelled three a day) |
|---|---|---|
| Brand Xenical 120 mg | $4.59 | $413.52 |
| Generic orlistat 120 mg | $7.07 | $636.04 |
Our arithmetic from NADAC unit costs. The generic costs pharmacies about 54% more than the brand, the reverse of the usual pattern; NADAC does not explain why. These are acquisition costs; counter prices differ. Alli is sold at retail and is not in this NADAC extract. GLP-1 cash prices are on GLP-1 cost.
What the record does not show
- Whether orlistat reduces heart attacks, strokes or deaths. The Xenical label states its long-term effects on obesity-related illness and death "have not been established".
- Any comparison with, or combination with, a GLP-1 medicine. No trial is on either label.
- Why the generic is dearer than the brand in the pharmacy cost survey.
Xenical is a prescription medicine and Alli carries its own warnings panel. Whether orlistat, a GLP-1 medicine or neither suits a person's digestion, medicines and history is a decision for their prescriber or pharmacist.
Sources
- XENICAL (orlistat) 120 mg capsules, US prescribing information, H2-Pharma, effective 9 January 2026, set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e (openFDA drug label record), read 3 November 2026 — sections 1, 2, 4, 5, 6.1, 12.2, 14.
- ALLI (orlistat 60 mg) Drug Facts, Haleon US Holdings, effective 18 March 2026, set ID a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f (openFDA), read 3 November 2026.
- Drugs@FDA (openFDA): NDA 020766 (XENICAL, approved 23 April 1999); NDA 021887 (ALLI, over the counter, approved 7 February 2007). Read 3 November 2026.
- Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. "XENical in the prevention of diabetes in obese subjects (XENDOS) study." Diabetes Care 2004;27(1):155–61, doi:10.2337/diacare.27.1.155, PMID 14693982.
- Wilding JPH et al., NEJM 2021, PMID 33567185 (STEP 1). Jastreboff AM et al., NEJM 2022, PMID 35658024 (SURMOUNT-1). CONTRAVE prescribing information, effective 10 November 2025 — section 14.
- NADAC (National Average Drug Acquisition Cost) 2026, Centers for Medicare & Medicaid Services, data.medicaid.gov, as-of date 21 October 2026, read 3 November 2026.