What does the research show about orlistat?

Orlistat

Across trials of a year or more, orlistat cut about 2 to 3 kg more weight than placebo. Over 4 years it lowered new diabetes from 9.0% to 6.2%, mostly in people with impaired glucose tolerance. LDL cholesterol fell slightly. Oily spotting, urgency and fecal incontinence were common. Rare liver and kidney injury reports appear on the label.

Add to Bio HackChecked 2026-11-09

Status: FDA-approved for weight loss in the US. Xenical (120 mg) is a prescription drug for chronic weight management. Alli (60 mg) is sold over the counter as a weight loss aid for adults.
Also called: Xenical, Alli, tetrahydrolipstatin, lipase inhibitor
Taken for: weight loss, fat blocking, cholesterol, diabetes prevention, fatty liver

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

StrongShown to cut about 2 to 3 kg more weight than placebo over a year, the smallest effect of five obesity drugs compared.Very common
StrongShown to lower total and LDL cholesterol slightly, by about 0.3 mmol/L, with larger drops when more weight was lost.
StrongShown to lower liver enzymes in fatty liver disease, ALT by about 9 U/L. Liver fat and scarring were not measured.
LimitedOne trial found 37% fewer diabetes cases over 4 years in adults with obesity, explained by those with impaired glucose tolerance.

Reported risks5

StrongShown to raise oily spotting to 27% against 1% on placebo, with more fecal urgency, oily stools and incontinence.Very common
ModerateShown to raise stopping for side effects about 1.6 times over placebo, a 3% absolute difference, mostly from gut effects.How often is not known
LimitedThe label lists reports of severe liver injury, some ending in transplant or death. A UK study found injury rose before starting, which its authors tie to prior health changes.How often is not known
LimitedThe label warns of oxalate kidney stones and oxalate kidney damage with renal failure. One case report describes injury that improved after stopping.How often is not known
LimitedThe label warns orlistat can reduce the effect of drugs such as cyclosporine, levothyroxine and warfarin, and reduce absorption of some fat-soluble vitamins.How often is not known

What people take it for, and what was found

Shown to help4

StrongVery common

Weight loss

Shown to cut about 2 to 3 kg more weight than placebo over a year, the smallest effect of five obesity drugs compared.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Against placebo, orlistat reduced weight by 2.9 kg (95% CI 2.5 to 3.2) [1] and by 2.6 kg (95% CrI 2.16 to 3.04) at one year, the smallest effect of the five obesity drugs compared [2]. A loss of at least 5% occurred in 44% on orlistat against a median 23% on placebo [2]. A meta-analysis of 33 RCTs found a mean difference of 2.12 kg [3].
Population: 16 trials with 10,631 participants lasting 1 to 4 years [1]; 28 RCTs with 29,018 adults [2]; 33 RCTs with 9,732 participants [3].
Sources: [1], [2], [3]
Caveats: Attrition averaged 30 to 40% [1] and 30 to 45% [2]. The pooled trials mostly tested 120 mg three times daily with a reduced-calorie diet.

Limited

Type 2 diabetes onset

One trial found 37% fewer diabetes cases over 4 years in adults with obesity, explained by those with impaired glucose tolerance.

The numbers and sources

Effect: After 4 years, cumulative diabetes incidence was 9.0% on placebo and 6.2% on orlistat, a risk reduction of 37.3%. The effect was explained by the subgroup with impaired glucose tolerance. Weight loss was 5.8 kg on orlistat and 3.0 kg on placebo [4]. A meta-analysis of long-term trials also reported a lower incidence of diabetes on orlistat [1].
Population: 3,305 adults with BMI 30 or more, 21% with impaired glucose tolerance, over 4 years [4].
Sources: [4], [1]
Caveats: 52% on orlistat and 34% on placebo completed treatment. When dropouts' baseline weights were carried forward, weight loss was 3.6 kg against 1.4 kg [4].

Strong

Cholesterol and blood lipids

Shown to lower total and LDL cholesterol slightly, by about 0.3 mmol/L, with larger drops when more weight was lost.

The numbers and sources

Effect: Orlistat lowered total cholesterol by 0.30 mmol/L and LDL cholesterol by 0.27 mmol/L. HDL cholesterol fell 0.034 mmol/L and triglycerides 0.09 mmol/L. Lipoprotein(a) did not change. LDL lowering was larger with more weight loss and shorter treatment [3]. An earlier systematic review also found greater falls in total and LDL cholesterol than with control [5].
Population: 33 RCTs [3]; 28 RCTs, 17 of them with 10,041 patients over a year [5].
Sources: [3], [5]
Caveats: The changes are small. The reviews do not separate the drug from the weight lost.

Strong

Liver enzymes in fatty liver disease

Shown to lower liver enzymes in fatty liver disease, ALT by about 9 U/L. Liver fat and scarring were not measured.

The numbers and sources

Effect: In people with metabolic dysfunction-associated steatotic liver disease, orlistat lowered AST by 4.01 U/L (95% CI 1.97 to 6.05), ALT by 8.70 U/L (95% CI 0.90 to 16.51) and GGT by 7.74 U/L (95% CI 0.59 to 14.88) against control. LDL cholesterol fell 5.61 mg/dL, fasting glucose 4.05 mg/dL, HOMA-IR 0.70 and BMI 0.99 kg/m². Blood pressure did not change [6]. A second meta-analysis also found lower ALT, AST, HOMA-IR, BMI, cholesterol, insulin and waist circumference [7].
Population: 6 RCTs [6]; 11 studies with 582 participants [7].
Sources: [6], [7]
Caveats: Both reviews measured blood markers, not liver fat on imaging or scarring on biopsy. The trials were small and likely overlap between the reviews. The abstract of [7] does not say whether all 11 studies were randomized.

Doses studied

The long-term trials and XENDOS used 120 mg three times daily [4][5]. The over-the-counter product contains 60 mg per capsule [8].

Risks

Reported risks5

StrongVery common

Oily stools, urgency and fecal incontinence

Shown to raise oily spotting to 27% against 1% on placebo, with more fecal urgency, oily stools and incontinence.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: In the Xenical year-one trials, oily spotting occurred in 27% on orlistat and 1% on placebo. Flatus with discharge occurred in 24% against 1%, fecal urgency in 22% against 7%, fatty or oily stool in 20% against 3%, and fecal incontinence in 8% against 1% [9]. Pooled, gastrointestinal events were more common than on placebo (RR 1.46, 95% CI 1.37 to 1.55) [5].
Population: 1,913 on orlistat and 1,466 on placebo in seven 1- to 2-year trials [9]; 17 trials [5].
Sources: [9], [5]
Caveats: The label states these events may increase with a diet above 30% of calories from fat [9].

ModerateHow often is not known

Stopping treatment for side effects

Shown to raise stopping for side effects about 1.6 times over placebo, a 3% absolute difference, mostly from gut effects.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The risk of discontinuing for adverse events was 1.59 (95% CI 1.21 to 2.08) times that of placebo, a 3% absolute difference. Gastrointestinal events caused 40% of withdrawals [10]. A network meta-analysis found odds of 1.71 (95% CI 1.42 to 2.05) against lifestyle change alone [11].
Population: 16 orlistat trials of 12 to 24 months [10]; 132 RCTs with 48,209 adults [11].
Sources: [10], [11]
Caveats: [10] included placebo-controlled trials at licensed doses and excluded weight maintenance trials.

LimitedHow often is not known

Liver injury

The label lists reports of severe liver injury, some ending in transplant or death. A UK study found injury rose before starting, which its authors tie to prior health changes.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Xenical label lists postmarketing reports of severe liver injury with hepatocellular necrosis or acute liver failure, some ending in transplant or death [9]. The Alli label notes rare reports of liver injury [8]. In a self-controlled case series, liver injury incidence was raised in the 90 days before starting (IRR 1.50) and the first 30 days after (IRR 2.21), then returned to baseline. The first 90 days on treatment did not differ from the 90 days before (IRR 1.02, 95% CI 0.67 to 1.56) [12].
Population: Postmarketing reports [8][9]; 94,695 orlistat users in UK primary care, 988 liver injury cases [12].
Sources: [9], [8], [12]
Caveats: The authors of [12] state the timing points to the health changes that led to starting treatment rather than a drug effect. Case reports cannot give a rate.

LimitedHow often is not known

Kidney injury from oxalate

The label warns of oxalate kidney stones and oxalate kidney damage with renal failure. One case report describes injury that improved after stopping.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Xenical label warns of oxalate kidney stones and oxalate nephropathy with renal failure [9]. A case report describes acute kidney injury with calcium oxalate crystals on biopsy in a woman with chronic kidney disease after an orlistat dose increase, improving after it was stopped [13].
Population: Postmarketing reports [9]; one patient [13].
Sources: [9], [13]
Caveats: No trial measured this as an outcome.

LimitedHow often is not known

Reduced absorption of other drugs and fat-soluble vitamins

The label warns orlistat can reduce the effect of drugs such as cyclosporine, levothyroxine and warfarin, and reduce absorption of some fat-soluble vitamins.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Xenical label reports serious outcomes from loss of effect of cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs and antiretroviral drugs taken with orlistat, and reduced absorption of some fat-soluble vitamins and beta carotene [9]. The Alli label lists organ transplant and cyclosporine use as reasons not to use it [8].
Population: Postmarketing reports and interaction data in the label [8][9].
Sources: [9], [8]
Caveats: Label statements, not trial rates.

Sources

Rucker D, Padwal R, Li SK, et al. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007. https://doi.org/10.1136/bmj.39385.413113.25
Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events. JAMA. 2016. https://doi.org/10.1001/jama.2016.7602
Sahebkar A, Simental-Mendía LE, Reiner Ž, et al. Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials. Pharmacological Research. 2017. https://doi.org/10.1016/j.phrs.2017.05.022
Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study. Diabetes Care. 2004. https://doi.org/10.2337/diacare.27.1.155
Hutton B, Fergusson D. Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. The American Journal of Clinical Nutrition. 2004. https://doi.org/10.1093/ajcn/80.6.1461
Karimi M, Pourfaraji SMA, Parhizkar Roudsari P, Pirzad S. Efficacy of Orlistat on Cardiometabolic Indices in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A GRADE-Assessed Systematic Review and Meta-Analysis of RCTs. Current Therapeutic Research. 2026. https://doi.org/10.1016/j.curtheres.2026.100822
Ayati A, Vahed IE, Rahimi Y, et al. Efficacy of orlistat for the treatment of metabolic dysfunction-associated steatotic liver disease patients: A systematic review and meta-analysis. Hepatology Forum. 2025. https://doi.org/10.14744/hf.2024.2024.0047
U.S. Food and Drug Administration. ALLI (orlistat 60 mg capsule), over-the-counter drug facts label. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f
U.S. Food and Drug Administration. XENICAL (orlistat) capsules, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6240792b-9224-2d10-e053-2a91aa0a2c3e
Johansson K, Neovius K, DeSantis SM, et al. Discontinuation due to adverse events in randomized trials of orlistat, sibutramine and rimonabant: a meta-analysis. Obesity Reviews. 2009. https://doi.org/10.1111/j.1467-789X.2009.00581.x
Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. The Lancet. 2024. https://doi.org/10.1016/S0140-6736(24)00351-9
Douglas IJ, Langham J, Bhaskaran K, et al. Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink. BMJ. 2013. https://doi.org/10.1136/bmj.f1936
Singh A, Sarkar SR, Gaber LW, Perazella MA. Acute Oxalate Nephropathy Associated With Orlistat, a Gastrointestinal Lipase Inhibitor. American Journal of Kidney Diseases. 2007. https://doi.org/10.1053/j.ajkd.2006.10.004

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