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Orlistat is a capsule swallowed with meals. It is not a hormone and does not act on the brain or on appetite — it irreversibly blocks gastric and pancreatic lipases, the enzymes that digest fat, by forming a covalent bond with their active serine residue. Roughly a third of the fat in a meal leaves the body in the stool instead of being absorbed. Systemic absorption is negligible (source-facts describe the medicine as “local, not systemic” and “act[ing] only inside the gut”), so the medicine acts entirely inside the gut. In the EU it is sold as Xenical and taken alongside a slightly reduced-calorie, lower-fat diet.
Orlistat 120mg vs. alli. This page covers the prescription-strength 120 mg capsule (Xenical) that Hi Doctor’s doctors review. alli is the pharmacy version of orlistat that can be bought without a prescription — each alli capsule contains half the orlistat dose of the prescription-only 120 mg product. alli is centrally authorised across the EU, and the authorisation is held by Haleon Ireland Dungarvan Limited.

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What it is

Active ingredient

Orlistat — a lipase inhibitor taken as a hard capsule that acts only inside the gut.

Dosage

120 mg with each main meal, up to three capsules a day.
Orlistat is authorised in the EU for weight loss in adults with obesity, alongside a mildly reduced-calorie diet, and specifically for a body mass index of 28 kg/m² or more, taken together with a mildly reduced-calorie, lower-fat diet. It has been authorised for use in the EU since 29 July 1998, so a licensed doctor can prescribe it when it is clinically appropriate.

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How it works

It switches off fat-digesting enzymes

Orlistat blocks the enzymes in the stomach and gut that break down fat, so about a third of the fat in a meal passes through the body instead of being absorbed.

Dietary fat stays undigested

The inactivated enzyme cannot break dietary fat, which arrives as triglycerides, into the smaller free fatty acids and monoglycerides that the gut wall can take up. The fat stays whole, and whole fat molecules are too large to cross into the body.

The blocked fat leaves in stool

The unabsorbed fat passes along the bowel and out in the stool, so those calories never reach the body. The European Medicines Agency describes the 120 mg dose as letting about 30% of the fat eaten in a meal pass through undigested.
Unlike GLP-1 medicines, orlistat does not act on appetite — its effect depends on keeping to an appropriate diet while taking it. It is a valid alternative for people who cannot or do not want injectable treatments, although average weight loss is usually lower.

No injections

A capsule, not an injection.

Local, not systemic

Acts locally in the gut, not system-wide.

Adjunct to diet

An alternative when GLP-1s aren’t the right fit.

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What the studies reported

XENDOS was a 4-year, double-blind, prospective trial that randomised patients with obesity (BMI ≥30) to lifestyle changes plus orlistat 120 mg or placebo three times daily. The co-primary endpoints were time to onset of type 2 diabetes and change in body weight, analysed by intention to treat. Only 52% of the orlistat group and 34% of the placebo group completed the four years. The cumulative incidence of diabetes was lower with orlistat than placebo, with a risk reduction that was statistically significant, and the mean weight loss was greater with orlistat (P<0.001 for both comparisons). The diabetes-prevention effect was driven largely by the subgroup with impaired glucose tolerance at baseline, and the trial did not measure cardiovascular outcomes (Diabetes Care 2004;27(1):155-161; PMID 14693982, confirmed by web fetch).
Every trial behind orlistat is grouped by source and evidence grade, so journal data and manufacturer announcements are not confused.

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Beyond weight loss: lipid effects

Because orlistat blocks the absorption of dietary fat, it also reduces the absorption of cholesterol carried in that fat. In the European Multicentre trial, total cholesterol and LDL-cholesterol fell more in the orlistat group than in the placebo group, even after adjusting for weight loss alone (The Lancet 1998; PMID 9683204, confirmed by web fetch). However, this lipid benefit is secondary to the weight-loss indication and is not itself a licensed treatment target; the reviewing doctor considers the primary reason for prescribing.

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Who it is not suitable for

A doctor checks medical history and current medication before prescribing. Yellowing skin can signal serious liver injury and should always be reported. Orlistat is contraindicated in chronic malabsorption syndrome and cholestasis; in the latter, the reduced biliary secretion means that the lipase-blocking mechanism cannot be relied upon. Orlistat is not recommended in pregnancy because the maternal weight loss it produces may harm fetal growth, and it is not known whether the medicine or its metabolites pass into breast milk. No dose adjustment is needed in renal impairment because the medicine is minimally absorbed. The EU product information does not specify dose adjustment for hepatic impairment, though caution is advised in patients with pre-existing liver disease because rare cases of liver injury have been reported.

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Interactions explained by mechanism

Because orlistat forms a covalent bond with the active serine residue of gastric and pancreatic lipases, the enzymes are irreversibly inactivated for the duration of their transit through the gut. This physical blockade of fat digestion means that any lipophilic medicine whose absorption depends on being carried in mixed micelles — such as cyclosporine, amiodarone, and some antiepileptic medicines — may have reduced bioavailability when taken at the same time as orlistat. The EU Summary of Product Characteristics advises that orlistat and cyclosporine should not be taken together, and that thyroid medicines, warfarin and some anti-epileptic medicines may need dose adjustment. The fat-soluble vitamins A, D, E and K are similarly affected because their intestinal uptake requires micellar solubilisation. The EU product information recommends a multivitamin supplement taken at bedtime, at least 2 hours after the last orlistat dose. The reviewing doctor checks current medication before prescribing.

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Population specifics

Orlistat is contraindicated in chronic malabsorption syndrome and cholestasis. There is limited data in pregnancy — orlistat is not recommended during pregnancy because the maternal weight loss it produces may harm fetal growth, and it is not known whether the medicine or its metabolites pass into breast milk. No dose adjustment is needed in renal impairment; the medicine acts locally in the gut and is minimally absorbed. The EU product information does not specify dose adjustment for hepatic impairment, though caution is advised in patients with pre-existing liver disease because rare cases of liver injury have been reported.

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What happens when you stop

Because orlistat works only while it is in the gut, stopping means normal fat digestion resumes. Weight that was lost during treatment can be regained if the dietary changes made alongside it are not sustained.

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Common questions

Orlistat and GLP-1 medicines work through completely different mechanisms — one in the gut, one through hormone signalling. A doctor reviews whether combining them is appropriate for your case, but the two are not routinely prescribed together.
The effect on fat absorption starts with the first capsule taken with a fatty meal. Weight change is reviewed at month 3 by the doctor, as the first meaningful assessment point.
Yes. Orlistat is authorised alongside a mildly reduced-calorie, lower-fat diet. The bowel effects are more likely after a fatty meal, so adjusting meals towards lower fat from day 1 is part of the approach.
Orlistat can reduce absorption of vitamins A, D, E and K. The EU product information advises a diet rich in fruit and vegetables and says a multivitamin supplement taken at bedtime may be considered.
Orlistat has been authorised for use in the EU since 29 July 1998, with long-term safety data from the XENDOS trial that followed people for four years. The doctor reviews response at month 3 and periodically thereafter.

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What has been reported

The EU Summary of Product Characteristics lists these bowel effects at the 120 mg dose: These bowel effects are more likely after a fatty meal, because the undigested fat has to go somewhere.
Orlistat can reduce absorption of vitamins A, D, E and K. The EU product information advises a diet rich in fruit and vegetables, and says a multivitamin supplement — taken at bedtime — may be considered.

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How Hi Doctor handles it

A questionnaire covering weight, medical history, current medication and previous weight-loss treatment feeds into the doctor’s decision — see how eligibility works. Orlistat is one of several weight-loss options a doctor may consider, alongside injectable medicines like Mounjaro and Wegovy. For the 120 mg prescription version, see orlistat (Xenical). The medical consultation cost is set out on pricing; the medicine itself is paid separately at a pharmacy. See also safety and eligibility for the full checks a doctor applies.

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Start a consultation

Weight-loss consultation

Answer the weight-loss questionnaire and a registered doctor reviews it. They decide whether treatment is appropriate, which one, and at what dose — and declining is a normal outcome. See what it costs and how the review works.
This page is reference information, not medical advice and not a prescription. Whether a medicine is appropriate for you is decided by a registered doctor after reviewing your consultation.