Alli (orlistat) for weight loss: does it work?

If you’ve been exploring options for weight loss, you’ve probably come across Alli. Unlike drugs like Wegovy, which is a prescription weight loss medication, Alli (generic name orlistat) can be purchased over-the-counter. But how effective is it? 

Read on to understand how Alli works, the side effects you can expect, and everything else you need to know.

Alli (orlistat) is an over-the-counter medication that is FDA-approved for weight loss in overweight adults. It’s designed to be used in combination with a reduced-calorie, low-fat diet to help people lose weight. In this context, “low-fat” means fewer than 30% of your calories should come from fat, and “reduced-calorie” means eating about 500 fewer calories per day than usual. 

Alli is an oral medication that contains 60 mg of orlistat, the drug’s active ingredient. The medication is meant to be taken up to three times a day, each time within 1 hour after eating a meal containing fat. Each pack of Alli contains 60 capsules, which is around a 20-day supply. 

Because Alli can reduce the absorption of certain vitamins, doctors recommend adding a daily multivitamin that contains vitamins A, D, E, K and beta-carotene at least two hours after taking Alli. GlaxoSmithKline, the makers of Alli, recommend taking your multivitamin at night.

The same active ingredient in Alli, orlistat, is available in a stronger dose in a prescription medication called Xenical (which is twice the dosage––120 mg per pill). Like Alli, Xenical is intended to be used in combination with a reduced-calorie diet and can help people lose weight. It may also be prescribed to prevent weight gain in people who recently lost a lot of weight. Some studies have calculated that the 60 mg dosage of orlistat in Alli is about 85% as effective as the prescription-strength 120 mg dosage of Xenical.

The short answer is yes, Alli (orlistat) can help you lose weight. According to the makers of Alli, for every five pounds you lose through dietary changes, Alli can help you lose an additional two to three pounds. Everyone loses weight at different rates and many different factors affect how much weight you lose in a given period of time, but clinical studies showed that over a period of six months, participants using orlistat had an added weight loss of around five to ten pounds.

Following a reduced-calorie diet, which is a crucial component of treatment with Alli, will help you lose weight. Adding Alli into the mix essentially helps you lose more weight faster, especially when combined with exercise. 

In clinical studies, people taking Alli have lost both body weight and belly fat. In one study, at the end of a two-year weight loss program, participants who took Alli lost significantly more weight and fat than those taking a placebo. In particular, they reduced their visceral adipose tissue (belly fat) by nearly 16%, while those on the placebo only lost about 9.5%. Visceral fat is the kind of belly fat associated with an increased risk of heart disease and metabolic conditions.

In a study of U.S. Army soldiers, those treated with Alli in addition to dietary modifications lost about half a pound more than those using a placebo. Importantly, however, those taking Alli primarily lost the weight from fat, while those on the placebo lost more weight from muscle. Losing too much lean muscle mass can cause your metabolism — and consequently your weight loss — to slow down, resulting in a weight loss plateau. That’s why it’s important to supplement any weight loss plan with plenty of protein and strength training exercises. Both help you build muscle and keep your metabolism up.

Alli (orlistat) works by reducing the amount of fat your body absorbs from each meal. After you eat, enzymes in your digestive system known as lipases digest the fat you ate by breaking down triglycerides into free fatty acids and monoglycerides that your body can absorb. Orlistat is a type of lipase inhibitor, meaning it prevents your body from breaking down those fat molecules by inhibiting these lipase enzymes from doing their job. As a result, the free fatty acids don’t get absorbed, and instead continue along your digestive tract where they exit as waste instead. Overall, orlistat reduces the amount of dietary fat you absorb by about 30%.

Orlistat may also help lower your body mass index (BMI), waist circumference, and cholesterol, including LDL cholesterol. The amount of weight loss people achieve with orlistat has also been shown to slightly lower blood pressure.

Alli (orlistat) starts working immediately but it can take about two weeks after you start taking it to start to see weight loss. Usually people start to notice significant weight loss after they’ve been taking Alli for at least two months. The majority of the weight loss occurs in the first six months on the medication. 

Alli is most effective when combined with a low-fat diet and exercise. Diet and exercise may look different for different people and it’s a good idea to lay out a plan with your doctor, but in one study, participants taking Alli reduced their caloric intake by 500 calories daily, and committed to walking for 30–45 minutes five times a week.

Like many medications, you can expect some side effects when taking Alli (orlistat). Alli reduces your body’s absorption of fat, causing the fat to leave your body as waste (in bowel movements) instead. As a result, you may notice some changes related to your bowel movements, including:

• Gas with oily spotting 

• Loose or oily stools

• More frequent stools that may be hard to control

• Diarrhea

• Abdominal pain

• Anal fissures

Following a low-fat diet can help reduce these side effects of orlistat. For most people, symptoms subside with time as your body gets used to the medication.

While rare, some people may experience serious side effects while taking Alli, including gallstones, pancreatitis, and kidney or liver problems. If you experience any of the following, stop taking Alli and contact a healthcare professional:

• Severe skin Itching

• Yellow eyes or skin

• Dark urine

• Loss of appetite

• Severe or persistent abdominal pain

• Difficulty breathing or swallowing

Also, people who take seizure medication should stop taking Alli if they start to experience more frequent or intense seizures.

While Alli (orlistat) is well-tolerated by many people, it is not safe for everyone. Specifically, you should not use Alli (orlistat) if you:

• Have had an organ transplant

• Have a history of malabsorption syndrome

• Have a history of gallbladder problems, kidney stones, or pancreatitis

• Have an eating disorder, including anorexia or bulimia

• Are pregnant or breastfeeding

• Are taking cyclosporine

• Are not overweight

• Are allergic to orlistat or any of the inactive ingredients in Alli (these include FD&C Blue No. 2, edible ink, gelatin, iron oxide, microcrystalline cellulose, povidone, sodium lauryl sulfate, sodium starch glycolate, talc, and titanium dioxide)

Alli should not be used by people who are not overweight. If you’re not sure if your body weight qualifies you for Alli, the label on the package contains a weight and height chart you can reference. 

If you are taking any of the prescription medications below, you’ll want to check with your healthcare provider before starting Alli to ensure it will be safe for you. They may need to adjust your dosage or recommend extra monitoring while taking Alli. Or, they may advise you to use a different weight loss medication altogether..

• Amiodarone

• Cyclosporine

• Blood thinners like warfarin

• Thyroid medications like levothyroxine

• Diabetes medications

• Antiepileptic medications like gabapentin

• Antiretrovirals for HIV

• Any other weight loss supplements or medications

In general, it’s a good idea to check with a health provider before starting any new medication or supplement, even if it’s over-the-counter. They can help ensure it will be safe for you based on your medical history, underlying health conditions, and current medications. They may also recommend something that could work better for your weight loss goals. 

Alli (orlistat) does lead to weight loss, but as an over-the-counter medication, it may lead to less weight loss than certain prescription medications. Here’s a quick overview of FDA-approved options for weight loss. (P.S. Non-FDA approved supplements that claim to help you lose weight quickly are like get-rich-quick schemes: you should avoid them.)

• Xenical (orlistat) is a prescription-strength version of orlistat, with 120 mg per tablet vs. the 60 mg Alli contains. Side effects are similar to Alli, and may include increased defecation, or flatulence with oily discharge. Among a group of individuals with obesity, people lost an average 4.6% of their body weight within six months of taking Xenical.

• Wegovy (semaglutide) is an injectable prescription medication that is administered once a week. People taking Wegovy have been shown to lose nearly 11% of their body weight, on average, within six months. Gastrointestinal side effects are common with Wegovy, including nausea, vomiting, and diarrhea.

• Saxenda (liraglutide) is another injectable prescription medication for weight loss, with similar gastrointestinal side effects to Wegovy. However, it is injected on a daily basis. Studies have found that people may lose 7% of their body weight, on average, within six months of starting Saxenda. Around one-third lose more than 10% of their body weight in the same time frame.

• Qsymia (phentermine/topiramate) is a prescription stimulant and appetite suppressant. Side effects include prickling or tingling feelings, dizziness, changes in taste, insomnia, constipation, and dry mouth. In a study that compared Qsymia with orlistat, participants taking Qsymia lost 4% of their body weight within 5 months, while those taking orlistat lost 2%. As a stimulant containing phentermine, a Schedule IV controlled substance, Qsymia carries a risk of abuse and dependence. 

• Contrave (naltrexone/bupropion) is a twice-daily oral medication for weight loss. Side effects may include gastrointestinal side effects like nausea, vomiting, and diarrhea, as well as headache, dizziness, insomnia, and dry mouth. Studies show that people tend to lose at least 5% of their body weight within 6–12 months of taking Contrave.

You may need to meet certain body weight or BMI requirements to qualify for these medications, or have a weight-related health condition like type 2 diabetes or high blood pressure. They’re all intended to be used in combination with lifestyle changes like diet and exercise.

The above medications can support long-term weight loss. The FDA has also approved four weight loss pills for short-term use, up to a period of 12 weeks. These include:

• Phentermine

• Benzphetamine

• Diethylpropion

• Phendimetrazine

These medications work by suppressing your appetite. They contain controlled substances as their active ingredients, which means there can be an increased risk for abuse and dependence when using them, and may make them even riskier for people with certain underlying conditions, like cardiovascular disease, glaucoma, and hypertension. 

If you’ve been struggling to lose weight through lifestyle changes like diet and exercise, a weight loss medication can help. Talk to your healthcare provider about your options and what might be a good fit for you.

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Current version

August 29, 2023

Written by

Amelia Willson

Fact checked by

Yael Cooperman, MD

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About the medical reviewer

Yael Cooperman, MD, Ro

Yael Cooperman is a physician and works as a Senior Manager, Medical Content & Education at Ro.