Orlistat

updated

Orlistat is an FDA-approved lipase inhibitor sold as prescription XENICAL (1999) and over-the-counter alli (2007). The label states it blocks approximately 30% of dietary fat absorption at the prescription regimen, and the weight effect is modest: 13.4 lb versus 5.8 lb on placebo at 1 year in pooled label data, with a reduced-calorie diet in every arm.

Gastrointestinal lipase inhibitor

  • FDA approved XENICAL (NDA 020766) on 23 April 1999 and the over-the-counter alli (NDA 021887) on 7 February 2007; both are orlistat.
  • The XENICAL label states orlistat inhibits dietary fat absorption by approximately 30% at the recommended prescription regimen.
  • In pooled one-year label data from five trials, mean weight loss was 13.4 lb on XENICAL versus 5.8 lb on placebo, with a reduced-calorie diet in every arm.
  • In XENDOS (3304 obese adults, 4 years), type 2 diabetes incidence was 5.5% versus 8.3% on placebo (p=0.01), driven by people with impaired glucose tolerance.
  • A network meta-analysis of 28 trials in 29,018 adults placed orlistat last of five approved agents at 1 year, with 2.6 kg excess weight loss over placebo.
  • In year 1, oily spotting occurred in 26.6% on XENICAL versus 1.3% on placebo.

What is orlistat approved to do?

FDA approved orlistat as prescription XENICAL in 1999 for obesity management and as over-the-counter alli in 2007 as a weight loss aid. Both products contain the same molecule at different strengths.

XENICAL is labeled for obesity management, including weight loss and weight maintenance with a reduced-calorie diet, and to reduce the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. FDA approved it under NDA 020766 on 23 April 1999.

alli is the over-the-counter product, labeled as a weight loss aid for overweight adults 18 and older who also follow a reduced-calorie and low-fat diet. FDA approved it under NDA 021887 on 7 February 2007. It carries half the prescription strength per capsule and is not the product studied in XENDOS.

Orlistat, also called tetrahydrolipstatin, is C29H53NO5 (495.7 g/mol, CAS 96829-58-2). Xenical and alli are listed synonyms for one molecule, so the two products differ in strength and labeling, not in substance.

XENICAL label, version effective 9 January 2026: indication, mechanism, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

The label approves XENICAL for obesity management, including weight loss and weight maintenance with a reduced-calorie diet and reducing the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. Orlistat is a reversible inhibitor of gastrointestinal lipases that forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL); in therapeutic studies detection was sporadic at below 10 ng/mL without accumulation. In seven double-blind placebo-controlled trials, year 1 adverse events on XENICAL (n=1913) versus placebo (n=1466) were oily spotting 26.6% versus 1.3%, flatus with discharge 23.9% versus 1.4% and fecal urgency 22.1% versus 6.7%. In year 2 (n=613 versus 524) they were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism. It contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption, interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs, rare severe liver injury with hepatocellular necrosis or acute hepatic failure, oxalate nephrolithiasis and oxalate nephropathy, a higher cholelithiasis risk with substantial weight loss, exclusion of organic causes of obesity such as hypothyroidism, and more gastrointestinal events on a diet above 30% of calories from fat. The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia.

Participants / model
Adults meeting the label BMI criteria; human volunteers for the dose-response and PK data; adults in seven double-blind placebo-controlled trials and postmarketing reports
Treatment
XENICAL 120 mg oral capsules
Follow-up
Label version effective 9 January 2026
Study design
FDA prescribing information
Funding
not stated in the source

The roughly 30% fat-absorption figure belongs to the prescription regimen and should not be transferred to the over-the-counter capsule. Liver injury and oxalate nephropathy are label warnings; this page gives no incidence figure for them.

Read the original source
alli label, version effective 18 March 2026: over-the-counter indication and transplant alert

Official label

DailyMed, U.S. National Library of Medicine. alli (orlistat) 60 mg oral capsules, non-prescription label, version effective 18 March 2026. Set ID a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f.

alli is the over-the-counter product: orlistat 60 mg per sealed capsule, with the purpose stated as a weight loss aid, for weight loss in overweight adults 18 years and older when used along with a reduced-calorie and low-fat diet. The label carries an organ transplant alert telling people who have had a transplant not to use it because orlistat interferes with anti-rejection medicines, and says not to use it with cyclosporine. It is half the prescription strength per capsule and is not the product studied in XENDOS.

Participants / model
Overweight adults 18 and older
Treatment
alli orlistat 60 mg oral capsules, non-prescription
Follow-up
Label version effective 18 March 2026
Study design
Official over-the-counter label
Funding
not stated in the source

No XENDOS or pooled-trial weight result should be attributed to alli.

Read the original source
Drugs@FDA: XENICAL 1999, alli 2007

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020766 (XENICAL), with NDA 021887 (alli). Dates read from the openFDA Drugs@FDA records.

FDA approved XENICAL under NDA 020766 on 23 April 1999 and alli under NDA 021887 on 7 February 2007. Both are orlistat; the prescription and non-prescription routes to market are separate applications.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1999 to 2007
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels.

Read the original source
PubChem: orlistat identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 3034010 (orlistat, tetrahydrolipstatin).

Orlistat, also called tetrahydrolipstatin: C29H53NO5, 495.7 g/mol, CAS 96829-58-2. Xenical and alli are listed synonyms for the same single molecule, so the prescription and over-the-counter products differ in strength and labeling, not in substance.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the weight-loss studies find?

In pooled one-year label data, mean weight loss was 13.4 lb on XENICAL versus 5.8 lb on placebo, with a reduced-calorie diet in every arm. A network meta-analysis of 28 trials placed orlistat last of five approved agents at 1 year.

In pooled data from five trials in the XENICAL label, mean weight loss over 1 year in the intent-to-treat population was 13.4 lb on XENICAL versus 5.8 lb on placebo, a mean difference of 3% of body weight. Completion was 69% on XENICAL and 63% on placebo. Of those who completed the year, 57% on XENICAL and 31% on placebo lost at least 5% of baseline body weight. Every arm included a reduced-calorie diet and nutritional counseling.

A network meta-analysis of 28 randomized trials in 29,018 overweight and obese adults compared the FDA-approved long-term weight-loss agents at 1 year. At least 5% weight loss occurred in 44% on orlistat (odds ratio 2.70, 95% CrI 2.34 to 3.09) versus a median 23% on placebo, against 75% for phentermine-topiramate and 63% for liraglutide. Excess weight loss versus placebo was 2.6 kg for orlistat, against 8.8 kg for phentermine-topiramate and 5.3 kg for liraglutide. Attrition of 30 to 45% in all trials lowered confidence in the estimates.

XENICAL label trial data: 13.4 lb versus 5.8 lb at 1 year; XENDOS 3304 adults, 4 years

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, clinical studies section, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

In pooled data from five clinical trials, mean weight loss over 1 year in the intent-to-treat population was 13.4 lb on XENICAL versus 5.8 lb on placebo, a mean percent weight loss difference of 3%. Completion was 1072 XENICAL patients (69%) and 701 placebo patients (63%). Of those completing 1 year, 57% on XENICAL and 31% on placebo lost at least 5% of baseline body weight. Every arm included a reduced-calorie diet and nutritional counseling. In XENDOS (3304 obese patients aged 30 to 58 with normal or impaired glucose tolerance), completion was 52% of 1649 XENICAL patients and 34% of 1655 placebo patients. At 4 years mean weight loss was -5.17% on XENICAL versus -2.75% on placebo (p<0.001), and cumulative incidence of type 2 diabetes was 5.5% versus 8.3% (p=0.01). The diabetes finding was driven by patients with impaired glucose tolerance at baseline; XENICAL did not reduce diabetes risk in those with normal glucose tolerance. Four-year changes, XENICAL versus placebo: total cholesterol -7.02% versus -2.03%, LDL -11.66% versus -3.85%, systolic blood pressure -4.12 versus -2.60 mm Hg, waist circumference -5.78 versus -3.99 cm. The label states that long-term effects on obesity-related morbidity and mortality have not been established.

Participants / model
Over 2,800 patients on XENICAL and 1,400 on placebo across seven long-term trials (age 17 to 78, 80.2% women); 3304 obese adults aged 30 to 58 in XENDOS
Treatment
XENICAL 120 mg capsules plus a reduced-calorie diet and nutritional counseling
Follow-up
1 year (pooled trials) and 4 years (XENDOS)
Study design
Label summary of placebo-controlled trials and the XENDOS trial
Funding
not stated in the source

Every arm included diet and counseling. These results do not apply to alli, which is not the product studied in XENDOS.

Read the original source
Network meta-analysis: 28 trials, 29,018 adults, orlistat last of five at 1 year

Systematic review and meta-analysis

Khera R et al. JAMA. 2016;315(22):2424-34. PMID 27299618.

At 1 year, orlistat placed last of the five approved agents compared. At least 5% weight loss: 44% on orlistat (odds ratio 2.70, 95% CrI 2.34 to 3.09, SUCRA 0.22) versus a median 23% on placebo, against 75% for phentermine-topiramate and 63% for liraglutide. Excess weight loss versus placebo was 2.6 kg for orlistat (95% CrI -3.04 to -2.16), against 8.8 kg for phentermine-topiramate and 5.3 kg for liraglutide. The authors noted attrition of 30 to 45% in all trials and lower confidence in the estimates as a result.

Participants / model
29,018 overweight and obese adults across 28 randomized trials (median age 46, 74% women, median baseline weight 100.5 kg, median BMI 36.1)
Treatment
Oral orlistat and four comparator agents, at least 1 year
Follow-up
At least 1 year
Study design
Systematic review and network meta-analysis of randomized trials
Funding
not stated in the source

Attrition of 30 to 45% in all trials lowers confidence in the estimates.

Read the original source

What did the four-year XENDOS trial show?

In 3304 obese adults over 4 years, weight loss was 5.17% on XENICAL versus 2.75% on placebo, and type 2 diabetes appeared in 5.5% versus 8.3%. The diabetes benefit came from people with impaired glucose tolerance.

XENDOS enrolled 3304 obese patients aged 30 to 58 with normal or impaired glucose tolerance. Completion was 52% of 1649 XENICAL patients and 34% of 1655 placebo patients. At 4 years mean weight loss was 5.17% on XENICAL versus 2.75% on placebo (p<0.001). Cumulative type 2 diabetes incidence was 5.5% versus 8.3% (p=0.01).

The diabetes finding was driven by patients with impaired glucose tolerance at baseline. XENICAL did not reduce diabetes risk in those with normal glucose tolerance. Four-year changes on XENICAL versus placebo were total cholesterol -7.02% versus -2.03%, LDL -11.66% versus -3.85%, systolic blood pressure -4.12 versus -2.60 mm Hg and waist circumference -5.78 versus -3.99 cm.

The label states that long-term effects on obesity-related morbidity and mortality have not been established. XENDOS used the prescription product, not alli.

XENICAL label trial data: 13.4 lb versus 5.8 lb at 1 year; XENDOS 3304 adults, 4 years

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, clinical studies section, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

In pooled data from five clinical trials, mean weight loss over 1 year in the intent-to-treat population was 13.4 lb on XENICAL versus 5.8 lb on placebo, a mean percent weight loss difference of 3%. Completion was 1072 XENICAL patients (69%) and 701 placebo patients (63%). Of those completing 1 year, 57% on XENICAL and 31% on placebo lost at least 5% of baseline body weight. Every arm included a reduced-calorie diet and nutritional counseling. In XENDOS (3304 obese patients aged 30 to 58 with normal or impaired glucose tolerance), completion was 52% of 1649 XENICAL patients and 34% of 1655 placebo patients. At 4 years mean weight loss was -5.17% on XENICAL versus -2.75% on placebo (p<0.001), and cumulative incidence of type 2 diabetes was 5.5% versus 8.3% (p=0.01). The diabetes finding was driven by patients with impaired glucose tolerance at baseline; XENICAL did not reduce diabetes risk in those with normal glucose tolerance. Four-year changes, XENICAL versus placebo: total cholesterol -7.02% versus -2.03%, LDL -11.66% versus -3.85%, systolic blood pressure -4.12 versus -2.60 mm Hg, waist circumference -5.78 versus -3.99 cm. The label states that long-term effects on obesity-related morbidity and mortality have not been established.

Participants / model
Over 2,800 patients on XENICAL and 1,400 on placebo across seven long-term trials (age 17 to 78, 80.2% women); 3304 obese adults aged 30 to 58 in XENDOS
Treatment
XENICAL 120 mg capsules plus a reduced-calorie diet and nutritional counseling
Follow-up
1 year (pooled trials) and 4 years (XENDOS)
Study design
Label summary of placebo-controlled trials and the XENDOS trial
Funding
not stated in the source

Every arm included diet and counseling. These results do not apply to alli, which is not the product studied in XENDOS.

Read the original source

Is orlistat the only approved drug that blocks dietary fat absorption?

In US approval records, yes. An openFDA query on 9 October 2026 found no application for cetilistat, the other lipase inhibitor developed for obesity. The claim is accurate on mechanism and approval, but it leaves out the size of the result: 2.6 kg over placebo at 1 year.

Sellers describe orlistat as a lipase inhibitor that produces fat loss by blocking dietary fat absorption, and as the only FDA-approved compound that works this way. The mechanism is as the label describes, and the label quantifies the block at approximately 30% of dietary fat at the recommended prescription regimen.

On exclusivity, an openFDA exact-name query for cetilistat returned no matching application on 9 October 2026. That supports a narrow, dated, US-only statement that orlistat is the only FDA-approved gastrointestinal lipase inhibitor located. It says nothing about other countries.

The claim does not say how large the result is. The network meta-analysis found 2.6 kg of excess weight loss over placebo at 1 year, the lowest of the five approved agents compared. The roughly 30% fat-block figure belongs to the prescription regimen, and no source here extends it to the over-the-counter capsule.

openFDA query, 9 October 2026: no cetilistat application

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA exact-name query for cetilistat (brand and generic name fields), run on 9 October 2026.

Drugs@FDA holds approved applications for orlistat as a prescription product (NDA 020766) and a non-prescription product (NDA 021887). An openFDA exact-name query for cetilistat, the other gastrointestinal lipase inhibitor developed for obesity, returned no matching application on 9 October 2026. This supports a narrow, dated, US-only statement that orlistat is the only FDA-approved gastrointestinal lipase inhibitor located. It is not a worldwide statement and says nothing about approvals in other countries.

Participants / model
FDA application database, not a clinical population
Treatment
Exact substance-name query
Follow-up
Query run on 9 October 2026
Study design
Dated US approval-record query
Funding
not stated in the source

A negative query on one date is not proof about every product or jurisdiction.

Read the original source
Drugs@FDA: XENICAL 1999, alli 2007

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020766 (XENICAL), with NDA 021887 (alli). Dates read from the openFDA Drugs@FDA records.

FDA approved XENICAL under NDA 020766 on 23 April 1999 and alli under NDA 021887 on 7 February 2007. Both are orlistat; the prescription and non-prescription routes to market are separate applications.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1999 to 2007
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels.

Read the original source
XENICAL label, version effective 9 January 2026: indication, mechanism, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

The label approves XENICAL for obesity management, including weight loss and weight maintenance with a reduced-calorie diet and reducing the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. Orlistat is a reversible inhibitor of gastrointestinal lipases that forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL); in therapeutic studies detection was sporadic at below 10 ng/mL without accumulation. In seven double-blind placebo-controlled trials, year 1 adverse events on XENICAL (n=1913) versus placebo (n=1466) were oily spotting 26.6% versus 1.3%, flatus with discharge 23.9% versus 1.4% and fecal urgency 22.1% versus 6.7%. In year 2 (n=613 versus 524) they were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism. It contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption, interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs, rare severe liver injury with hepatocellular necrosis or acute hepatic failure, oxalate nephrolithiasis and oxalate nephropathy, a higher cholelithiasis risk with substantial weight loss, exclusion of organic causes of obesity such as hypothyroidism, and more gastrointestinal events on a diet above 30% of calories from fat. The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia.

Participants / model
Adults meeting the label BMI criteria; human volunteers for the dose-response and PK data; adults in seven double-blind placebo-controlled trials and postmarketing reports
Treatment
XENICAL 120 mg oral capsules
Follow-up
Label version effective 9 January 2026
Study design
FDA prescribing information
Funding
not stated in the source

The roughly 30% fat-absorption figure belongs to the prescription regimen and should not be transferred to the over-the-counter capsule. Liver injury and oxalate nephropathy are label warnings; this page gives no incidence figure for them.

Read the original source
Network meta-analysis: 28 trials, 29,018 adults, orlistat last of five at 1 year

Systematic review and meta-analysis

Khera R et al. JAMA. 2016;315(22):2424-34. PMID 27299618.

At 1 year, orlistat placed last of the five approved agents compared. At least 5% weight loss: 44% on orlistat (odds ratio 2.70, 95% CrI 2.34 to 3.09, SUCRA 0.22) versus a median 23% on placebo, against 75% for phentermine-topiramate and 63% for liraglutide. Excess weight loss versus placebo was 2.6 kg for orlistat (95% CrI -3.04 to -2.16), against 8.8 kg for phentermine-topiramate and 5.3 kg for liraglutide. The authors noted attrition of 30 to 45% in all trials and lower confidence in the estimates as a result.

Participants / model
29,018 overweight and obese adults across 28 randomized trials (median age 46, 74% women, median baseline weight 100.5 kg, median BMI 36.1)
Treatment
Oral orlistat and four comparator agents, at least 1 year
Follow-up
At least 1 year
Study design
Systematic review and network meta-analysis of randomized trials
Funding
not stated in the source

Attrition of 30 to 45% in all trials lowers confidence in the estimates.

Read the original source

How does orlistat work, and how much reaches the blood?

Orlistat blocks gastric and pancreatic lipases in the gut, so dietary triglycerides are not broken down for absorption. Very little intact drug reaches plasma.

Orlistat is a reversible inhibitor of gastrointestinal lipases. It forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping.

Systemic exposure is minimal. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL). In therapeutic studies detection was sporadic at below 10 ng/mL, without accumulation.

XENICAL label, version effective 9 January 2026: indication, mechanism, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

The label approves XENICAL for obesity management, including weight loss and weight maintenance with a reduced-calorie diet and reducing the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. Orlistat is a reversible inhibitor of gastrointestinal lipases that forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL); in therapeutic studies detection was sporadic at below 10 ng/mL without accumulation. In seven double-blind placebo-controlled trials, year 1 adverse events on XENICAL (n=1913) versus placebo (n=1466) were oily spotting 26.6% versus 1.3%, flatus with discharge 23.9% versus 1.4% and fecal urgency 22.1% versus 6.7%. In year 2 (n=613 versus 524) they were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism. It contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption, interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs, rare severe liver injury with hepatocellular necrosis or acute hepatic failure, oxalate nephrolithiasis and oxalate nephropathy, a higher cholelithiasis risk with substantial weight loss, exclusion of organic causes of obesity such as hypothyroidism, and more gastrointestinal events on a diet above 30% of calories from fat. The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia.

Participants / model
Adults meeting the label BMI criteria; human volunteers for the dose-response and PK data; adults in seven double-blind placebo-controlled trials and postmarketing reports
Treatment
XENICAL 120 mg oral capsules
Follow-up
Label version effective 9 January 2026
Study design
FDA prescribing information
Funding
not stated in the source

The roughly 30% fat-absorption figure belongs to the prescription regimen and should not be transferred to the over-the-counter capsule. Liver injury and oxalate nephropathy are label warnings; this page gives no incidence figure for them.

Read the original source

What side effects and warnings does the label report?

Oily spotting, flatus with discharge and fecal urgency were the most common adverse events, and the label contraindicates use in pregnancy and chronic malabsorption. Warnings cover vitamin absorption, drug interactions, rare severe liver injury and oxalate kidney injury.

In the label's seven double-blind placebo-controlled trials, year 1 oily spotting occurred in 26.6% on XENICAL versus 1.3% on placebo, flatus with discharge in 23.9% versus 1.4%, and fecal urgency in 22.1% versus 6.7%. In year 2 the rates were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism, and notes more gastrointestinal events on a diet above 30% of calories from fat.

The label contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption; interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs; rare severe liver injury with hepatocellular necrosis or acute hepatic failure; oxalate nephrolithiasis and oxalate nephropathy; and a higher cholelithiasis risk with substantial weight loss. Incidence figures for the liver and oxalate events are not given here.

The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia. The alli label carries an organ transplant alert because orlistat interferes with anti-rejection medicines, and says not to use it with cyclosporine.

XENICAL label, version effective 9 January 2026: indication, mechanism, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

The label approves XENICAL for obesity management, including weight loss and weight maintenance with a reduced-calorie diet and reducing the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. Orlistat is a reversible inhibitor of gastrointestinal lipases that forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL); in therapeutic studies detection was sporadic at below 10 ng/mL without accumulation. In seven double-blind placebo-controlled trials, year 1 adverse events on XENICAL (n=1913) versus placebo (n=1466) were oily spotting 26.6% versus 1.3%, flatus with discharge 23.9% versus 1.4% and fecal urgency 22.1% versus 6.7%. In year 2 (n=613 versus 524) they were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism. It contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption, interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs, rare severe liver injury with hepatocellular necrosis or acute hepatic failure, oxalate nephrolithiasis and oxalate nephropathy, a higher cholelithiasis risk with substantial weight loss, exclusion of organic causes of obesity such as hypothyroidism, and more gastrointestinal events on a diet above 30% of calories from fat. The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia.

Participants / model
Adults meeting the label BMI criteria; human volunteers for the dose-response and PK data; adults in seven double-blind placebo-controlled trials and postmarketing reports
Treatment
XENICAL 120 mg oral capsules
Follow-up
Label version effective 9 January 2026
Study design
FDA prescribing information
Funding
not stated in the source

The roughly 30% fat-absorption figure belongs to the prescription regimen and should not be transferred to the over-the-counter capsule. Liver injury and oxalate nephropathy are label warnings; this page gives no incidence figure for them.

Read the original source
alli label, version effective 18 March 2026: over-the-counter indication and transplant alert

Official label

DailyMed, U.S. National Library of Medicine. alli (orlistat) 60 mg oral capsules, non-prescription label, version effective 18 March 2026. Set ID a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f.

alli is the over-the-counter product: orlistat 60 mg per sealed capsule, with the purpose stated as a weight loss aid, for weight loss in overweight adults 18 years and older when used along with a reduced-calorie and low-fat diet. The label carries an organ transplant alert telling people who have had a transplant not to use it because orlistat interferes with anti-rejection medicines, and says not to use it with cyclosporine. It is half the prescription strength per capsule and is not the product studied in XENDOS.

Participants / model
Overweight adults 18 and older
Treatment
alli orlistat 60 mg oral capsules, non-prescription
Follow-up
Label version effective 18 March 2026
Study design
Official over-the-counter label
Funding
not stated in the source

No XENDOS or pooled-trial weight result should be attributed to alli.

Read the original source

Why does orlistat sit in S tier?

FDA approval for the labeled weight-loss use, long-term randomized trials and a large meta-analysis support the S. The effect is modest and gastrointestinal side effects are common.

The S applies to orlistat for obesity management, the use being sold. Behind it are seven placebo-controlled trials in the label, XENDOS in 3304 adults with a type 2 diabetes result at 4 years, and a 29,018-adult network meta-analysis.

The grade does not mean a large effect. Excess weight loss over placebo was 2.6 kg at 1 year, every trial arm paired the drug with a reduced-calorie diet and nutritional counseling, and the label states that long-term effects on obesity-related morbidity and mortality have not been established.

XENICAL label, version effective 9 January 2026: indication, mechanism, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

The label approves XENICAL for obesity management, including weight loss and weight maintenance with a reduced-calorie diet and reducing the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. Orlistat is a reversible inhibitor of gastrointestinal lipases that forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL); in therapeutic studies detection was sporadic at below 10 ng/mL without accumulation. In seven double-blind placebo-controlled trials, year 1 adverse events on XENICAL (n=1913) versus placebo (n=1466) were oily spotting 26.6% versus 1.3%, flatus with discharge 23.9% versus 1.4% and fecal urgency 22.1% versus 6.7%. In year 2 (n=613 versus 524) they were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism. It contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption, interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs, rare severe liver injury with hepatocellular necrosis or acute hepatic failure, oxalate nephrolithiasis and oxalate nephropathy, a higher cholelithiasis risk with substantial weight loss, exclusion of organic causes of obesity such as hypothyroidism, and more gastrointestinal events on a diet above 30% of calories from fat. The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia.

Participants / model
Adults meeting the label BMI criteria; human volunteers for the dose-response and PK data; adults in seven double-blind placebo-controlled trials and postmarketing reports
Treatment
XENICAL 120 mg oral capsules
Follow-up
Label version effective 9 January 2026
Study design
FDA prescribing information
Funding
not stated in the source

The roughly 30% fat-absorption figure belongs to the prescription regimen and should not be transferred to the over-the-counter capsule. Liver injury and oxalate nephropathy are label warnings; this page gives no incidence figure for them.

Read the original source
XENICAL label trial data: 13.4 lb versus 5.8 lb at 1 year; XENDOS 3304 adults, 4 years

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, clinical studies section, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

In pooled data from five clinical trials, mean weight loss over 1 year in the intent-to-treat population was 13.4 lb on XENICAL versus 5.8 lb on placebo, a mean percent weight loss difference of 3%. Completion was 1072 XENICAL patients (69%) and 701 placebo patients (63%). Of those completing 1 year, 57% on XENICAL and 31% on placebo lost at least 5% of baseline body weight. Every arm included a reduced-calorie diet and nutritional counseling. In XENDOS (3304 obese patients aged 30 to 58 with normal or impaired glucose tolerance), completion was 52% of 1649 XENICAL patients and 34% of 1655 placebo patients. At 4 years mean weight loss was -5.17% on XENICAL versus -2.75% on placebo (p<0.001), and cumulative incidence of type 2 diabetes was 5.5% versus 8.3% (p=0.01). The diabetes finding was driven by patients with impaired glucose tolerance at baseline; XENICAL did not reduce diabetes risk in those with normal glucose tolerance. Four-year changes, XENICAL versus placebo: total cholesterol -7.02% versus -2.03%, LDL -11.66% versus -3.85%, systolic blood pressure -4.12 versus -2.60 mm Hg, waist circumference -5.78 versus -3.99 cm. The label states that long-term effects on obesity-related morbidity and mortality have not been established.

Participants / model
Over 2,800 patients on XENICAL and 1,400 on placebo across seven long-term trials (age 17 to 78, 80.2% women); 3304 obese adults aged 30 to 58 in XENDOS
Treatment
XENICAL 120 mg capsules plus a reduced-calorie diet and nutritional counseling
Follow-up
1 year (pooled trials) and 4 years (XENDOS)
Study design
Label summary of placebo-controlled trials and the XENDOS trial
Funding
not stated in the source

Every arm included diet and counseling. These results do not apply to alli, which is not the product studied in XENDOS.

Read the original source
Network meta-analysis: 28 trials, 29,018 adults, orlistat last of five at 1 year

Systematic review and meta-analysis

Khera R et al. JAMA. 2016;315(22):2424-34. PMID 27299618.

At 1 year, orlistat placed last of the five approved agents compared. At least 5% weight loss: 44% on orlistat (odds ratio 2.70, 95% CrI 2.34 to 3.09, SUCRA 0.22) versus a median 23% on placebo, against 75% for phentermine-topiramate and 63% for liraglutide. Excess weight loss versus placebo was 2.6 kg for orlistat (95% CrI -3.04 to -2.16), against 8.8 kg for phentermine-topiramate and 5.3 kg for liraglutide. The authors noted attrition of 30 to 45% in all trials and lower confidence in the estimates as a result.

Participants / model
29,018 overweight and obese adults across 28 randomized trials (median age 46, 74% women, median baseline weight 100.5 kg, median BMI 36.1)
Treatment
Oral orlistat and four comparator agents, at least 1 year
Follow-up
At least 1 year
Study design
Systematic review and network meta-analysis of randomized trials
Funding
not stated in the source

Attrition of 30 to 45% in all trials lowers confidence in the estimates.

Read the original source
Drugs@FDA: XENICAL 1999, alli 2007

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020766 (XENICAL), with NDA 021887 (alli). Dates read from the openFDA Drugs@FDA records.

FDA approved XENICAL under NDA 020766 on 23 April 1999 and alli under NDA 021887 on 7 February 2007. Both are orlistat; the prescription and non-prescription routes to market are separate applications.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1999 to 2007
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels.

Read the original source

Studies and sources

PubChem: orlistat identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 3034010 (orlistat, tetrahydrolipstatin).

Orlistat, also called tetrahydrolipstatin: C29H53NO5, 495.7 g/mol, CAS 96829-58-2. Xenical and alli are listed synonyms for the same single molecule, so the prescription and over-the-counter products differ in strength and labeling, not in substance.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
XENICAL label, version effective 9 January 2026: indication, mechanism, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

The label approves XENICAL for obesity management, including weight loss and weight maintenance with a reduced-calorie diet and reducing the risk of weight regain after prior weight loss, in patients with a BMI at or above 30, or at or above 27 with other risk factors. Orlistat is a reversible inhibitor of gastrointestinal lipases that forms a covalent bond with the active serine site of gastric and pancreatic lipases, so dietary triglycerides are not hydrolysed to absorbable free fatty acids and monoglycerides. At the recommended prescription regimen the label states it inhibits dietary fat absorption by approximately 30%. The effect on fecal fat appears within 24 to 48 hours and returns to pretreatment levels within 48 to 72 hours of stopping. After an oral dose of 14C-orlistat, intact orlistat in plasma was near the limit of detection (below 5 ng/mL); in therapeutic studies detection was sporadic at below 10 ng/mL without accumulation. In seven double-blind placebo-controlled trials, year 1 adverse events on XENICAL (n=1913) versus placebo (n=1466) were oily spotting 26.6% versus 1.3%, flatus with discharge 23.9% versus 1.4% and fecal urgency 22.1% versus 6.7%. In year 2 (n=613 versus 524) they were 4.4% versus 0.2%, 2.1% versus 0.2% and 2.8% versus 1.7%. The label describes these events as primarily a manifestation of the mechanism. It contraindicates use in pregnancy, chronic malabsorption syndrome, cholestasis and known hypersensitivity. Warnings cover decreased vitamin absorption, interactions with cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs, rare severe liver injury with hepatocellular necrosis or acute hepatic failure, oxalate nephrolithiasis and oxalate nephropathy, a higher cholelithiasis risk with substantial weight loss, exclusion of organic causes of obesity such as hypothyroidism, and more gastrointestinal events on a diet above 30% of calories from fat. The label also notes potential for abuse in inappropriate populations such as patients with anorexia nervosa or bulimia.

Participants / model
Adults meeting the label BMI criteria; human volunteers for the dose-response and PK data; adults in seven double-blind placebo-controlled trials and postmarketing reports
Treatment
XENICAL 120 mg oral capsules
Follow-up
Label version effective 9 January 2026
Study design
FDA prescribing information
Funding
not stated in the source

The roughly 30% fat-absorption figure belongs to the prescription regimen and should not be transferred to the over-the-counter capsule. Liver injury and oxalate nephropathy are label warnings; this page gives no incidence figure for them.

Read the original source
XENICAL label trial data: 13.4 lb versus 5.8 lb at 1 year; XENDOS 3304 adults, 4 years

FDA prescribing information

DailyMed, U.S. National Library of Medicine. XENICAL (orlistat) 120 mg oral capsules, prescribing information, clinical studies section, label version effective 9 January 2026. Set ID 6240792b-9224-2d10-e053-2a91aa0a2c3e.

In pooled data from five clinical trials, mean weight loss over 1 year in the intent-to-treat population was 13.4 lb on XENICAL versus 5.8 lb on placebo, a mean percent weight loss difference of 3%. Completion was 1072 XENICAL patients (69%) and 701 placebo patients (63%). Of those completing 1 year, 57% on XENICAL and 31% on placebo lost at least 5% of baseline body weight. Every arm included a reduced-calorie diet and nutritional counseling. In XENDOS (3304 obese patients aged 30 to 58 with normal or impaired glucose tolerance), completion was 52% of 1649 XENICAL patients and 34% of 1655 placebo patients. At 4 years mean weight loss was -5.17% on XENICAL versus -2.75% on placebo (p<0.001), and cumulative incidence of type 2 diabetes was 5.5% versus 8.3% (p=0.01). The diabetes finding was driven by patients with impaired glucose tolerance at baseline; XENICAL did not reduce diabetes risk in those with normal glucose tolerance. Four-year changes, XENICAL versus placebo: total cholesterol -7.02% versus -2.03%, LDL -11.66% versus -3.85%, systolic blood pressure -4.12 versus -2.60 mm Hg, waist circumference -5.78 versus -3.99 cm. The label states that long-term effects on obesity-related morbidity and mortality have not been established.

Participants / model
Over 2,800 patients on XENICAL and 1,400 on placebo across seven long-term trials (age 17 to 78, 80.2% women); 3304 obese adults aged 30 to 58 in XENDOS
Treatment
XENICAL 120 mg capsules plus a reduced-calorie diet and nutritional counseling
Follow-up
1 year (pooled trials) and 4 years (XENDOS)
Study design
Label summary of placebo-controlled trials and the XENDOS trial
Funding
not stated in the source

Every arm included diet and counseling. These results do not apply to alli, which is not the product studied in XENDOS.

Read the original source
alli label, version effective 18 March 2026: over-the-counter indication and transplant alert

Official label

DailyMed, U.S. National Library of Medicine. alli (orlistat) 60 mg oral capsules, non-prescription label, version effective 18 March 2026. Set ID a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f.

alli is the over-the-counter product: orlistat 60 mg per sealed capsule, with the purpose stated as a weight loss aid, for weight loss in overweight adults 18 years and older when used along with a reduced-calorie and low-fat diet. The label carries an organ transplant alert telling people who have had a transplant not to use it because orlistat interferes with anti-rejection medicines, and says not to use it with cyclosporine. It is half the prescription strength per capsule and is not the product studied in XENDOS.

Participants / model
Overweight adults 18 and older
Treatment
alli orlistat 60 mg oral capsules, non-prescription
Follow-up
Label version effective 18 March 2026
Study design
Official over-the-counter label
Funding
not stated in the source

No XENDOS or pooled-trial weight result should be attributed to alli.

Read the original source
Drugs@FDA: XENICAL 1999, alli 2007

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020766 (XENICAL), with NDA 021887 (alli). Dates read from the openFDA Drugs@FDA records.

FDA approved XENICAL under NDA 020766 on 23 April 1999 and alli under NDA 021887 on 7 February 2007. Both are orlistat; the prescription and non-prescription routes to market are separate applications.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1999 to 2007
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels.

Read the original source
Network meta-analysis: 28 trials, 29,018 adults, orlistat last of five at 1 year

Systematic review and meta-analysis

Khera R et al. JAMA. 2016;315(22):2424-34. PMID 27299618.

At 1 year, orlistat placed last of the five approved agents compared. At least 5% weight loss: 44% on orlistat (odds ratio 2.70, 95% CrI 2.34 to 3.09, SUCRA 0.22) versus a median 23% on placebo, against 75% for phentermine-topiramate and 63% for liraglutide. Excess weight loss versus placebo was 2.6 kg for orlistat (95% CrI -3.04 to -2.16), against 8.8 kg for phentermine-topiramate and 5.3 kg for liraglutide. The authors noted attrition of 30 to 45% in all trials and lower confidence in the estimates as a result.

Participants / model
29,018 overweight and obese adults across 28 randomized trials (median age 46, 74% women, median baseline weight 100.5 kg, median BMI 36.1)
Treatment
Oral orlistat and four comparator agents, at least 1 year
Follow-up
At least 1 year
Study design
Systematic review and network meta-analysis of randomized trials
Funding
not stated in the source

Attrition of 30 to 45% in all trials lowers confidence in the estimates.

Read the original source
openFDA query, 9 October 2026: no cetilistat application

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA exact-name query for cetilistat (brand and generic name fields), run on 9 October 2026.

Drugs@FDA holds approved applications for orlistat as a prescription product (NDA 020766) and a non-prescription product (NDA 021887). An openFDA exact-name query for cetilistat, the other gastrointestinal lipase inhibitor developed for obesity, returned no matching application on 9 October 2026. This supports a narrow, dated, US-only statement that orlistat is the only FDA-approved gastrointestinal lipase inhibitor located. It is not a worldwide statement and says nothing about approvals in other countries.

Participants / model
FDA application database, not a clinical population
Treatment
Exact substance-name query
Follow-up
Query run on 9 October 2026
Study design
Dated US approval-record query
Funding
not stated in the source

A negative query on one date is not proof about every product or jurisdiction.

Read the original source

Why is Orlistat in S tier?

S fits an FDA-approved medicine used for its labeled purpose, with seven placebo-controlled trials behind the label, a 4-year randomized trial in 3304 adults and a network meta-analysis in 29,018 adults. The grade does not mean a large effect: the weight result is modest and gastrointestinal side effects are common.