FDA approved 1999·Roche (Xenical) / GSK (Alli OTC)

Orlistat

A capsule that blocks about a third of the fat you eat from being absorbed

Brand names: Xenical

Quick read · 5 min

WEIGHT LOSS
6.9%
~15 lbs for a 220 lb person
HOW YOU TAKE IT
Capsule 3× daily with meals
With each fat-containing meal — no injection
COST
$40–$400/month
OTC Alli ~$40–$60 · Rx Xenical ~$200–$400
MAIN SIDE EFFECT
Oily stools
About 3 in 10 people
MUSCLE IMPACT
Mostly fat mass
Most weight lost is typically fat mass
IF YOU STOP
Weight regain expected — no rebound hunger effect
Weight often returns — this is biology, not failure

People who tend to consider this:

  • Want the only non-prescription option (Alli OTC)
  • Prefer a non-hormonal approach that works in the gut, not the brain
  • Want the most affordable OTC option

This may not be right if:

Absolute contraindicationUse with caution
  • You eat a high-fat diet and are not willing to change it
  • You have chronic malabsorption or bile flow problems
  • You want significant weight loss

Not a complete list. Whether this treatment is right for you depends on factors only your doctor can assess.

Weight loss — what trials show

In the XENDOS trial, which ran for 4 years, people taking orlistat lost an average of about 6.9% of their body weight — roughly 15 lbs for a 220 lb person. The drug also reduced the risk of developing type 2 diabetes by 37% in that 4-year study. Orlistat has one of the longest published safety records of any weight loss medication.

These are averages from clinical trials — individual results vary. Trials compare the drug against a dummy pill, not against other weight loss drugs.

See the full trial data →

How this compares

Average weight loss in clinical trials. Not a ranking — individual results vary.

Orlistatyou're here6.9%(~15 lbs)
Semaglutide injection14.9%(~33 lbs)
Tirzepatide20.9%(~46 lbs)

Averages from clinical trials at highest approved dose. Not everyone achieves these results.

Lower average weight loss than newer medications, but available without a prescription in lower-dose OTC form (Alli 60mg).

What to expect — week by week

Day 1
Starts working immediately

Orlistat blocks fat absorption from the first dose. Effects on digestion begin right away.

Week 1–4
Digestive side effects may peak

Oily stools, urgency, and wind are most common early on. Following a low-fat diet significantly reduces these.

Month 2–3
~4% lost
Measurable weight loss

Weight effects begin from the first week (related to calorie malabsorption), but significant loss takes 8–12 weeks

Month 6+
~8.5% lost
Steady progress

Continued weight loss as long as dietary changes are maintained.

What happens if you stop?

Weight is typically regained after stopping. Unlike GLP-1 drugs, orlistat's effect is mechanical rather than hormonal, so there is no rebound hunger effect after stopping.

Weight trajectory — during treatment and after stopping

Pattern estimated — no large randomised withdrawal trial published for this drug.

100%-6.9%-2.4%On medicationAfter stoppingStartStopped1 year later

Most of the lost weight returns within a year of stopping — this is the body returning to its defended weight, not a failure. Long-term use or maintenance therapy can help preserve results.

See trial data on stopping →

Side effects

Frequencies from XENDOS. Most stomach and gut side effects are mild-to-moderate and peak during the dose increase period (first 12–16 weeks).

Side effectHow common

Percentages from XENDOS. Source: trial publication.

Important cautions
  • Rare cases of severe liver injury have been reported with orlistat. Tell your doctor immediately if you notice yellowing skin or eyes, dark urine, or itching.
  • Orlistat reduces absorption of fat-soluble vitamins (A, D, E, K). Take a daily multivitamin — at bedtime, at least 2 hours away from your orlistat dose.
  • Orlistat may reduce the absorption of some medications. Tell your doctor and pharmacist about all other medications you take.

This is not a complete list. Your doctor can advise based on your full medical history.

Muscle and lean mass

No specific body composition data distinguishes orlistat from calorie-restriction alone. The drug produces weight loss entirely through calorie malabsorption — lean mass effects depend on the degree of calorie deficit and protein intake.

What does the lost weight consist of?

Fat mass — the primary target of treatmentLean mass — muscle, bone, water

Resistance training (weight lifting, bodyweight exercises) can significantly reduce the lean mass portion. Aim for 2–3 sessions per week during weight loss.

Proportions estimated — detailed body composition data not available from published trials for this drug.

Cost & access

Rx ~$200–$400/month (Xenical); OTC ~$40–$60/month (Alli 60mg)

Requires a prescription from a licensed healthcare provider. Prices vary. Ask your doctor about savings programs.

Where this sits on the cost scaleLow cost
$0$350$700$1,050$1,400

~$40–$400/moper month (list price)

OTC version (Alli 60mg): ~$40–$60/month, no prescription needed. Prescription Xenical (120mg): ~$200–$400/month.

How to take it

  • Take one capsule three times daily — during each main meal that contains fat, or up to 1 hour after
  • If you skip a meal or eat a fat-free meal, skip that dose
  • Take a daily multivitamin at bedtime — at least 2 hours away from your orlistat doses
  • Stored at room temperature. No refrigeration needed.

How it works

Blocks pancreatic lipase enzymes in the small intestine, preventing approximately 30% of dietary fat from being broken down and absorbed. The undigested fat passes through the gut and is excreted, reducing calorie absorption.

Cardiovascular & other benefits

In the 4-year XENDOS trial, orlistat reduced progression from prediabetes to type 2 diabetes by 37% compared to placebo plus lifestyle changes. Modest improvements in blood pressure and LDL observed.

  • 37% reduction in progression to type 2 diabetes (XENDOS, 4 years)
  • Only approved obesity drug with a 4-year safety dataset
  • Available OTC at half dose (Alli 60 mg) — no prescription needed
  • Works in the gut — no central nervous system effects

Community insights

These are personal experiences shared in public online communities — not medical advice.

The GI side effects (oily leakage) are the mechanism — if you eat too much fat, the drug punishes you. Many people unintentionally adopt a low-fat diet and that's where some of the benefit comes from.

r/loseit·Shared when orlistat comes up in diet discussions

Wearing dark clothing or using panty liners is commonly mentioned as a practical tip, especially in the early weeks.

r/WeightLossAdvice·Practical advice from experienced users

Take a multivitamin every day — preferably at bedtime (away from your orlistat doses) because the drug reduces absorption of fat-soluble vitamins A, D, E, and K.

r/Saxenda·Safety tip shared across weight loss communities

Common questions

After reading this page, most people compare this with other medications, check if they qualify, or learn about side effects in more detail.

Next step most people take

Based on clinical trials · No rankings · Every claim linked to source

Last reviewed: March 2026

Medical disclaimer: This website is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any treatment.