List of lipase inhibitors: Uses, common brands, and safety information

Struggling with weight loss is a common challenge for millions of people worldwide, with almost 50% of adults in the U.S. alone having obesity. As dietary changes and exercise routines might not be enough, many people turn toward medications to help bridge the gap. Among these anti-obesity drugs, lipase inhibitors have been around for decades to help people achieve their weight-loss goals.

Orlistat, the only FDA-approved lipase inhibitor currently available, works differently than other weight-loss medications, making it a potential option for people living with obesity. Introduced in the late 1990s, this medication has stood the test of time as a tool for weight management. Still, researchers are continuing to explore and develop new lipase inhibitors.

What are lipase inhibitors?

Lipase inhibitors are substances that reduce the activity of lipases, which are enzymes found in our intestines. These enzymes are secreted by the pancreas when fat is present in our digestive system.

The most well-known lipase inhibitor is orlistat, a synthetic version of a naturally occurring substance called lipstatin. Scientists discovered lipstatin in bacteria, specifically a strain called Streptomyces toxytricini, and then modified it to create the medication we use today. 

Lipase inhibitors may come in different forms but are typically taken as prescription and OTC capsules. Alli is the OTC version of orlistat that comes as a 60 mg oral capsule, while Xenical is the prescription version that contains a higher strength of orlistat at 120 mg. It’s typically recommended to take these medications three times a day during or within an hour of eating a meal that contains fat.

How do lipase inhibitors work?

Lipase inhibitors have a unique mechanism of action, changing how the body handles fat from food. They block pancreatic and gastric lipases in the stomach and small intestine by binding to the active site of the lipase enzymes. Doing so prevents the enzyme from doing its job, which is to support the absorption of dietary fat. 

Here's a breakdown of what happens when you take a lipase inhibitor:

• Fats in your food, specifically triglycerides, don’t undergo lipid metabolism

• Around 30% of dietary fat isn’t absorbed in the gastrointestinal tract

• Undigested fat passes through the digestive system and is cleared through the stool

Normally, triglycerides are broken down by lipases into free fatty acids through a process called hydrolysis. By preventing the hydrolysis of dietary fats, lipase inhibitors reduce the accumulation of fatty acids in the body, which may help lower LDL cholesterol levels (often considered bad cholesterol) in the blood.

Natural products like fruits and vegetables also contain certain compounds inhibiting pancreatic lipase. For example, fruits like blueberries and strawberries may contain polyphenols that block lipase, similar to orlistat. However, these effects may be milder than prescription options like Xenical.

What are lipase inhibitors used for?

Lipase inhibitors are used to manage weight gain. By reducing fat absorption, they can help reduce weight in people with obesity or those who are overweight. Weight management may have various health benefits, including reducing the risks of cardiovascular diseases and events like heart attack and stroke.

Obesity management

Lipase inhibitors are mainly used to help with weight loss and weight management in people with obesity. These anti-obesity agents are most effective when combined with a reduced-calorie diet and regular exercise. Many doctors and healthcare providers prescribe them as part of a well-rounded plan that may include other weight-loss methods. 

Reducing weight regain

Many people struggle with keeping weight off once they've lost it. However, lipase inhibitors like orlistat can often help people maintain their body weight after successful weight loss. In addition to the treatment of obesity, orlistat is approved by the U.S. Food and Drug Administration (FDA) to prevent weight regain over time. They continue blocking fat absorption, making it easier for people to stick with their new, healthier weight.

Off-label uses

Lipase inhibitors sometimes have uses beyond their main purpose of weight management. Research suggests they can help people with heart failure who are also living with obesity. Some healthcare providers might prescribe them to lower triglycerides in certain patients, including children with type 1 hyperlipoproteinemia.

They might also benefit people with non-alcoholic fatty liver disease, showing improvements in some liver markers. However, the evidence isn't strong enough yet to make them the first choice for treating liver conditions. More research is still needed to fully understand all the potential benefits.

Who can take lipase inhibitors?

Lipase inhibitors are effective medications, but they’re not right for everyone. They’re typically reserved for adults and children 12 and older with a BMI (body mass index) of 30 or higher. They might also be recommended for those with a BMI of 27 to 29 with at least one weight-related condition, such as Type 2 diabetes, high cholesterol, or high blood pressure.

Can younger children take lipase inhibitors?

Orlistat is not approved for children under 12, and its safety and effectiveness have not been studied in children under 12. 

Can older adults take lipase inhibitors?

The use of lipase inhibitors in older adults hasn’t been sufficiently studied. Healthcare providers may prescribe lipase inhibitors to older adults if the benefits outweigh the potential risks. 

Can pregnant or breastfeeding women take lipase inhibitors?

Pregnant women should avoid taking lipase inhibitors like orlistat. This medication is classified as Pregnancy Category X, meaning it's not safe to use during pregnancy, as losing weight while pregnant can be harmful. Although animal studies showed no harmful effects on the developing fetus with high doses, the risks of weight loss to the baby are significant. As for breastfeeding, it is unclear whether orlistat passes into breast milk. Because of this uncertainty, caution is advised for nursing mothers considering this medication.

It's always important to discuss with a healthcare provider whether lipase inhibitors are an appropriate treatment. They can evaluate a person’s overall medical history, including current and past medications being taken and other health conditions. 

Are lipase inhibitors safe?

Recalls

There are no current recalls for lipase inhibitors

Restrictions

Certain people should not use lipase inhibitors like orlistat. These medications are contraindicated in people who are pregnant, those with chronic malabsorption syndrome, in which a person is unable to absorb dietary nutrients, and people with cholestasis, in which bile flow from the liver is blocked or slowed. In addition, lipase inhibitors should be avoided in people with a known allergy to any of their ingredients.

Before taking a lipase inhibitor, there are some warnings and precautions to keep in mind. Here are some potential risks to consider before starting treatment:

• Drug interactions: Orlistat can interact with some medications, including cyclosporine, levothyroxine, warfarin, and certain anticonvulsants and antiretroviral drugs. For example, taking orlistat with cyclosporine can lower its effectiveness, so they should not be taken at the same time. It's recommended to take cyclosporine at least 3 hours before or after orlistat. 

• Vitamin deficiencies: Orlistat can reduce the absorption of fat-soluble vitamins (like vitamins A, D, E, and K), which may lead to vitamin deficiencies. Therefore, taking a multivitamin supplement is recommended.

• Liver injury: There have been rare reports of severe liver issues in people using orlistat, some of which have led to serious outcomes. It's important to be aware of symptoms like loss of appetite, itching, yellowing of the skin or eyes, dark urine, light-colored stools, or pain in the upper right side of the abdomen. If these occur, stop taking orlistat and seek medical attention.

• Kidney problems: Some users may experience increased oxalate levels in their urine, leading to kidney stones or kidney problems. Those with existing kidney issues or a history of kidney stones should have their kidney function monitored while using orlistat.

• Gallstones: Rapid weight loss from using orlistat may increase the risk of gallstones. In studies, a higher percentage of people taking orlistat experienced gallstones than those who did not.

Before starting treatment with orlistat, it's important to rule out any underlying conditions causing obesity, such as thyroid problems. Following a healthy diet is also key. Consuming a high-fat diet while on orlistat can lead to more gastrointestinal adverse effects, so it’s best to spread fat intake across three meals each day to reduce these effects.

Are lipase inhibitors controlled substances?

No, lipase inhibitors are not controlled substances.

Common lipase inhibitor side effects

• Oily or fatty stools

• Oily rectal discharge (with a clear, orange, or brown color)

• Passing gas accompanied by oily discharge

• Increased frequency of bowel movements

• Urgent need to have a bowel movement

• Difficulty controlling bowel movements (fecal incontinence)

How much do lipase inhibitors cost?

Lipase inhibitors can vary widely in price depending on the brand, dosage, and whether you have insurance coverage. With insurance coverage, the cost of orlistat can depend on your specific insurance plan. Many insurers may require prior authorization for lipase inhibitors since they're weight loss medications.

Without insurance, Xenical could cost around $940 for a month’s supply. The over-the-counter version, Alli, may be more affordable for some at an average price of $91 per bottle. A generic version may be available, with prices varying depending on the manufacturer and pharmacy where it’s purchased. For those without insurance, pharmacy discount cards and manufacturer coupons can sometimes help reduce these costs.

It may be worth comparing prices at different pharmacies, as costs for these lipase inhibitor medications can differ. Online pharmacy comparison tools may help you find the best prices in your area. In addition, SingleCare offers a free prescription discount card that could save you up to 80% on brand-name and generic medications at pharmacies across the U.S.

Sources

• Current trends and future prospects of lipstatin: a lipase inhibitor and pro-drug for obesity, RSC Advances (2015)

• Orlistat, a new lipase inhibitor for the management of obesity, Pharmacotherapy (2018)

• Lipase inhibitors for obesity: A review, Biomedicine & Pharmacotherapy (2020)

• Highlights of prescribing information, U.S. Food and Drug Administration (2022)

• Orlistat, StatPearls (2024)

• Orlistat, Drugs and Lactation Database (2021)

• The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers, The Journal of Clinical Pharmacology (1996)

• Orlistat, LiverTox (2020)