Orlistat for Weight Loss: How Does Orlistat Work

Discover how Orlistat can support your weight loss journey and help you take control of your health. Learn about common side effects and interactions.

Table of Contents
  • What Is Orlistat?
  • How Does Orlistat Work?
  • Orlistat for Weight Loss
  • Information About Orlistat
  • Administration and Dosage
  • Side Effects
  • Cost and Coverage
  • Where Can I Learn More?

Orlistat for Weight Loss

You may have heard of Orlistat (Alli or Xenical) before. Scroll down to learn more about Orlistat and weight loss to see if it is the right medication.

What is Orlistat?

Orlistat is a prescription weight loss medication on the market for some time. It has helped patients who have struggled with obesity to lose weight for many years. It is sold under two brand names: Alli and Xenical. Alli is the over-the-counter version of Orlistat that is usually a lower dose. Xenical is a prescription medication that is given at a higher dose. Though this medication can be bought over the counter, you should always take it with the guidance of a medical professional.

How Does Orlistat Work?

Orlistat works by inhibiting the action of an enzyme called lipase found in the gut, which is responsible for breaking down dietary fats into smaller molecules that the body can absorb. By inhibiting lipase, orlistat prevents some of the fat consumed from being absorbed by the body, and instead, it passes through the digestive system and is excreted in the stool.

Who Qualifies for Orlistat?

Orlistat can be used for the treatment of obesity. If you have a BMI greater than or equal to 30 or a BMI greater than 27 with at least one other weight-related condition (diabetes, high blood pressure, high cholesterol), you may be eligible for this medication.

Though Orlistat can be bought over the counter, you should always take this medication with the guidance of a medical professional. There are potential side effects that your provider must be aware of, such as vitamin deficiencies;

Can Orlistat Be Used For Weight Loss?

Orlistat has been on the market for weight loss for over two decades. A study published back in 1998 looked into how effective Orlistat was on weight loss and preventing weight regain for patients struggling with obesity (1). Participants were given 120 mg of Orlistat and placed on a calorie-restricted diet (600kcal/day deficit) for 52 weeks. When the study concluded, participants taking orlistat lost around 10.3 kg (22 lbs) after the year, significantly more than the placebo group. When the placebo group was started on Orlistat and monitored for an additional year, they noticed an additional 0.9kg loss in weight.

However, due to the side effects and the existence of newer and more effective medications, some providers may recommend starting a different medication before offering Orlistat.

Orlistat vs Other Prescription Weight Loss Medications

Orlistat vs GLP-1 Medications

The GLP-1 agonist medications were all made to treat type 2 diabetes. They mimic the effects of the naturally produced hormone, GLP-1, released from cells in the gut to regulate blood sugar and slow food movement through the gut. There are many different kinds of GLP-1 agonist medications on the market today. Some are FDA-approved to treat obesity (Wegovy, Saxenda), while others can be used off-label for weight loss (Mounjaro, Ozempic, Rybelsus, Victoza, Trulicity).

These medications have gained popularity for their weight loss effects in recent years. They are more effective than Orlistat. In an observational study published in 2019, researchers compared Xenical to Saxenda, a type of GLP-1 agonist (2). They found that Saxenda led to greater weight loss effects, with participants taking Saxenda losing around 7.7 kg (~17 lbs) after six months. Also, more people achieved at least a 5% reduction in body weight with Saxenda than with Orlistat (65.7% for Saxenda vs 27.4% for Orlistat). This was seen in combination with diet and exercise.

Other studies on GLP-1 medications for weight loss have shown an even greater effect than the ones seen in the study above. Therefore, most GLP-1 agonists will perform better than Orlistat.

Orlistat vs Phentermine

Phentermine is another type of prescription weight loss medication. It is a stimulant that acts on the sympathetic nervous, which controls the “fight or flight” response in the body. It works by stimulating this system enough to reduce appetite and food cravings while increasing the energy the body uses, thus, more calories burned.

In a study published in 2006 in Korea, researchers examined the short-term weight loss effects of Phentermine for patients struggling with obesity (3). Participants were given phentermine and education on lifestyle modifications (diet and exercise) for 14 weeks. They saw that Phentermine reduced body weight (average of 6-7 kgs) and waist circumference after 14 weeks.

Comparing these results to the long-term studies done with Orlistat, it appears that Orlistat may lead to a more significant and sustainable weight loss effect than Phentermine. Orlistat may also be better for patients with heart conditions such as arrhythmias. Phentermine is also a controlled substance with the potential for addiction and abuse. Therefore, patients with a history of substance use disorder may benefit from Orlistat over Phentermine.

Orlistat vs Contrave

Contrave is a prescription weight loss medication that combines two medications: Bupropion and Naltrexone. Bupropion is an antidepressant, and Naltrexone is an opioid antagonist. Together, they work to reduce appetite and food cravings, leading to weight loss.

In the COR-1 trial, researchers wanted to examine how effectively Contrave managed obesity. The participants were given oral Contrave for 52 weeks, a calorie-restricted diet, and regular exercise (4). The results showed that after 52 weeks, almost half the participants taking Contrave saw at least a 5% reduction in weight. After this trial, multiple clinical trials followed that further showed the benefits of Contrave for weight loss.

Orlistat and Contrave effectively help with weight loss in patients struggling with obesity. Since Contrave includes an antidepressant, it may benefit patients who may be depressed or want to stop smoking. However, Contrave is not currently FDA-approved to treat depression or assist with smoking cessation.

Orlistat vs Qsymia

Qsymia is a prescription weight loss medication that contains a combination of two drugs: phentermine and topiramate. Phentermine is an appetite suppressant that affects the central nervous system and helps to reduce food cravings. Topiramate is an anti-seizure drug that can also help with weight loss by reducing appetite and increasing feelings of fullness. It also increases the effects of phentermine.

In the CONQUER Trial published in 201, researchers examined how effective Qsymia was at treating obesity. The study was done over a 52-week period where participants took different doses of Qysemia from 7.5mg/46mg to 15mg/92mg and looked at how their weight changed. They saw that people on 7.5 mg of Qysemia saw a 7.8% decrease, and this was seen without regular dieting and exercise! They also saw that around 68% of people noticed at least a 5% reduction in weight after one year (5).

Orlistat and Qysmia are both effective at managing obesity. However, Orlistat may be better for those with heart conditions like arrhythmias.

Orlistat Side Effects

One of the down sides of Orlistat is the many unfavorable side effects that patients may experience. This includes:

  • Stomach Pain
  • Oily or Fatty stools
  • Oily spotting in underwear
  • Gas
  • Loose stools

These side effects are usually temporary and may decrease in severity the longer you take Orlistat.

Orlistat Dosage and Administration

Orlistat can be given in a prescription form (Xenical) or over-the-counter form (Alli). Xenical is started as a 120 mg pill taken three times a day with each main meal that contains fat.  Alli is given as a 60mg pill in the same manner. Either form should be taken during a meal or up to one hour after. If a meal has no fat, then you can skip the dose.

This medication must be taken with a nutritionally balanced, reduced-calorie diet containing approximately 30% of calories from fats. It is also important to ensure you efficiently take fat-soluble vitamin supplements (D, E, A, and K) to prevent deficiency. Also, you may benefit from taking supplements or eating foods that contain healthy fats, such as Omega 3 and Omega 6 fatty acids. For best results, you should also engage in regular exercise of about 150 minutes per week.

Orlistat Contraindications and Warnings

Severe Allergic Reaction

You may experience a severe allergic reaction to Orlistat when first taking it. Signs of a severe allergic reaction include swelling of your face, lips, tongue, or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, and very rapid heartbeat. Let your provider know immediately if you have experienced this when taking Orlistat in the past.

Chronic Malabsorption

Chronic Malabsorption can occur in diseases that affect the abilty of your gut to absorb nutrients. Causes of Chronic Malabsorption include:

  • Celiac Disease
  • Inflammatory Bowel Disease (Ulcerative Colitis, Crohn's Disease)
  • Whipple Disease
  • Damage to intestines from Radiation
  • Parasitic Infections
  • Surgery that removes parts of the small intestine (bariatric surgery, cancer surgery)
  • Chronic Alcohol Abuse

Since Orlistat can prevent the absorption of vitamins and essential fats, you may want to avoid this medication if you do have a history of chronic malabsorption.


The Gallbladder is an organ under the liver that helps digest fats. When there is fat in the gut, it releases bile to help the intestines break down and absorb the fat. Since Orlistat prevents fat absorption, more fat will be in the intestines. With more fat in the intestines, more bile is released. Rapid weight loss can also increase the risk of gallstone formation.

If you have a history of gallstones, there is a greater chance that one of these stones will get stuck when leaving the gallbladder. This can cause painful inflammation of the gallbladder. If you have a gallstones or gallbladder disease history, you may want to avoid taking Orlistat.

Anorexia or Bulimia

There is the potential for the abuse of Orlistat by people suffering from eating disorders such as Anorexia or Bulimia. For this reason, it is important to inform your provider if you have an eating disorder before starting Orlistat.


There are limited studies of the use of Orlistat in pregnant patients. The weight loss effects of Orlistat may offer no benefit to pregnant people and potentially harm the fetus. Also, the risk of vitamin and nutrient deficiency may pose a risk to the fetus as well. Let your provider know if you are pregnant or plan on becoming pregnant before starting Orlistat.

Severe Kidney Disease

Patients with severe kidney disease are at risk of developing oxalate kidney stones when taking Orlistat. Your provider may want to monitor certain tests that look at kidney function while you are taking Orlistat. If you have a history of severe kidney disease, you should avoid Orlistat.

Drug Interactions

Orlistat can decrease the absorption of certain medications. One of these medications is Warfarin. If you are taking Orlistat while on warfarin, you do have the potential to bleed more easily. Make sure to review all of your medications with your provider before starting Orlistat.

Orlistat Coverage and Cost

Orlistat is available over the counter or as a prescription medication. The over-the-counter version, Alli, can cost around $50-$65 for a 30-day supply. Xenical can cost up to $555 for a 30-day supply. For this reason, your provider may recommend starting with Alli. You may be eligible for a Xenical Coupon to help cover the price.

Where Can I Get Orlistat?

If you would like to learn more about Orlistat or want to see if you might be eligible for medication-assisted weight loss, check out Mochi Health, where board-certified obesity medicine physicians can offer expertise in this realm!

Mochi Health is a virtual obesity medicine practice that connects you with medical providers, like licensed physicians and nurse practitioners, to help you optimize your weight loss journey. We provide monthly video chats with actual medical providers to provide guidance about weight management and to get you started on prescription weight loss medications to supplement your weight loss plan.


  1. Sjöström L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HP, Krempf M. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet. 1998 Jul 18;352(9123):167-72. doi: 10.1016/s0140-6736(97)11509-4. PMID: 9683204.
  2. Gorgojo-Martínez JJ, Basagoiti-Carreño B, Sanz-Velasco A, Serrano-Moreno C, Almodóvar-Ruiz F. Effectiveness and tolerability of orlistat and liraglutide in patients with obesity in a real-world setting: The XENSOR Study. Int J Clin Pract. 2019 Nov;73(11):e13399. doi: 10.1111/ijcp.13399. Epub 2019 Aug 19. PMID: 31397946.
  3. Kim KK, Cho HJ, Kang HC, Youn BB, Lee KR. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people. Yonsei Med J. 2006 Oct 31;47(5):614-25. doi: 10.3349/ymj.2006.47.5.614. PMID: 17066505; PMCID: PMC2687747.
  4. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605. doi: 10.1016/S0140-6736(10)60888-4. Epub 2010 Jul 29. Erratum in: Lancet. 2010 Aug 21;376(9741):594. Erratum in: Lancet. 2010 Oct 23;376(9750):1392. PMID: 20673995.
  5. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, Day WW. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Apr 16;377(9774):1341-52. doi: 10.1016/S0140-6736(11)60205-5. Epub 2011 Apr 8. Erratum in: Lancet. 2011 Apr 30;377(9776):1494. PMID: 21481449.

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