High cholesterol is when you have too much LDL, often called “bad” cholesterol, in your blood. Cholesterol is a waxy, fat-like substance your body needs to build cells and make hormones. But too much LDL can build up inside your blood vessels over time, raising the risk of a heart attack or stroke.
High cholesterol usually does not cause symptoms, so many people do not know they have it until it shows up in a blood test. Diet, physical activity, body weight, and genetics are all factors that can contribute to high cholesterol.
Several medicines can lower LDL cholesterol, including statins, ezetimibe, and PCSK9 inhibitors. In July 2026, the FDA approved Lipfendra (enlicitide) as the first PCSK9-blocking medicine that is taken by mouth rather than injection.
Keep reading this article to learn how Lipfendra works for high cholesterol and about its benefits seen in studies. You may also be interested in reading about Lipfendra side effects and interactions .
How Does Lipfendra Work to Lower Cholesterol?
Your liver naturally removes bad cholesterol (LDL) from your blood using proteins called LDL receptors. Another protein in your body, called PCSK9, limits how well this process works. PCSK9 does so by lowering the number of LDL receptors available to clear LDL cholesterol.
Lipfendra works by blocking PCSK9. This allows more LDL receptors to remain on the surface of liver cells. This allows them to remove more LDL cholesterol from your blood. As a result, LDL cholesterol levels go down.
Lowering LDL cholesterol is important because high LDL can build up inside your arteries over time. This buildup, called plaque, can increase the risk of serious problems such as a heart attack or stroke.
Is Lipfendra Right for My High Cholesterol?
Lipfendra is FDA-approved for people with high cholesterol (hypercholesterolemia), including those with heterozygous familial hypercholesterolemia (HeFH). HeFH is an inherited condition that causes very high LDL cholesterol levels from birth, making it harder to reach healthy cholesterol levels through lifestyle changes alone.
Lipfendra is used along with a heart-healthy diet and regular physical activity.
When deciding whether Lipfendra may be right for you, your health care provider may consider several things, such as your cholesterol levels, your risk of having a heart attack or stroke, and other cholesterol medicines you take.
Your health care provider can help decide whether Lipfendra is a good option for you. For example, this medicine may be an option if your LDL cholesterol remains too high despite taking a statin or other cholesterol-lowering medicines or if you cannot take those medicines. It may also be an option if you prefer a pill over an injectable PCSK9 inhibitor and your health care provider recommends switching. They will guide you through any changes to your treatment plan.
How Was Lipfendra Studied for Lowering Cholesterol?
Two clinical trials were done to test how well Lipfendra works for lowering LDL cholesterol. Trial 1 included adults with high cholesterol who had already had a heart attack, stroke, or another cardiovascular event or those who were at increased risk for one. Trial 2 included adults with HeFH, an inherited condition that causes very high LDL cholesterol levels.
Trial 1 included 2,909 adults with high cholesterol from 14 countries.
- Participants ranged in age from 19 to 89 years, and their average age was 63. Nearly half (47%) were 65 or older.
- About 39% were women, and 61% were men.
- More than half (54%) were White, 26% were Asian, 11% identified as more than one race, 9% were Black or African American, and less than 1% were American Indian or Alaska Native.
- About 28% of participants identified as Hispanic or Latino.
- About 58% had previously had a major cardiovascular event, such as a heart attack or stroke.
- Almost everyone (97%) was already taking a statin, and about 1 in 4 were also taking ezetimibe or a medicine similar to ezetimibe.
Trial 2 included 303 adults with HeFH from 17 countries.
- These participants ranged in age from 20 to 84 years, and the average age was 52.
- About half were women (51%), and half were men (49%).
- About 70% were White, 17% were Asian, 11% identified as more than one race, and 3% were Black or African American. About 21% identified as Hispanic or Latino.
- About 27% had previously had a major cardiovascular event, such as a heart attack or stroke.
- All participants were taking a statin, and nearly two-thirds (64%) were also taking ezetimibe.
People could not join the studies if they had uncontrolled high blood pressure, uncontrolled diabetes, active liver disease, recent use of another PCSK9 inhibitor, or very high triglyceride levels.
In both studies, participants were randomly assigned to take either Lipfendra or a placebo (a tablet with no active medicine) once daily for a year (52 weeks). Everyone continued following a cholesterol-lowering diet and their usual cholesterol medicines, unless their doctor made medically necessary changes. Neither the participants nor the researchers knew who received Lipfendra until the studies were completed.
What Are the Benefits of Lipfendra Based on Studies?
The main goal of the studies was to measure the change in LDL (“bad”) cholesterol after 24 weeks of treatment. The researchers also measured LDL at the end of the 52-week study. They also looked at the levels of other fats in the blood to see if they changed during the study.
Results in adults with high cholesterol. In trial 1, people taking Lipfendra lowered their LDL cholesterol by an average of 57% after 24 weeks. In comparison, people taking a placebo saw a slight increase (about 3%) in their LDL cholesterol.
At the end of the study, people taking Lipfendra still had LDL cholesterol levels that were about 55% lower than when they started treatment. This shows that Lipfendra maintained its LDL-lowering effect throughout the full 52 weeks.
Results in adults with HeFH. Trial 2 results showed similar benefits in people with inherited high cholesterol (HeFH). After 24 weeks, participants taking Lipfendra lowered their LDL cholesterol by an average of 58%, while those taking a placebo saw a slight increase (about 3%) in their LDL cholesterol. The LDL reduction was maintained through 52 weeks.
Overall, both trials showed that Lipfendra worked better than a placebo to lower LDL cholesterol.
Also, people taking Lipfendra in both trials saw improvements in several other types of cholesterol and blood fats linked to heart disease. However, the studies were not designed to show whether lowering these levels with Lipfendra cuts the risk of heart attack, stroke, or death.
Your results may be different from what was seen in studies.
Is There Any Cost Assistance Available for Lipfendra?
Merck, the maker of Lipfendra, offers a cost assistance program that may allow eligible people to pay as little as $15 per prescription. Eligibility may depend on your insurance coverage. Visit www.lipfendra.com to learn more about Lipfendra copay savings. You can also call Merck at 800-727-5400 for more information.
