Key takeaways
Lipfendra is the first FDA-approved oral PCSK9 inhibitor used alongside diet and exercise to lower LDL cholesterol.
Lipfendra differs from statins in how it lowers LDL cholesterol, and the two types of medication can be used together.
Lipfendra was well-tolerated in clinical trials, though some people may experience mild side effects including diarrhea and dizziness.
If you have high cholesterol and are exploring your medication options, there is a new kid on the block. In July 2026, the U.S. Food and Drug Administration (FDA) approved Lipfendra (enlicitide), a once-daily pill that works differently from your typical statin to reduce low-density lipoprotein cholesterol (LDL-C).
Unlike statins, which reduce your liver’s cholesterol production, Lipfendra blocks a protein known as PCSK9, which helps the liver remove more cholesterol from the blood. It is the first oral PCSK9 inhibitor to receive approval from the FDA. Here’s what you should know about Lipfendra, including how it works, what the benefits are, and its potential side effects.
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What is Lipfendra?
Lipfendra is an oral PCSK9 inhibitor manufactured by Merck to treat high cholesterol. Other PCSK9 inhibitors, such as Repatha and Praluent, are injectable medications. Lipfendra is the first tablet of its kind. It’s intended to be used as an adjunct to diet and exercise to reduce LDL cholesterol (aka the “bad cholesterol”), which can lead to conditions like atherosclerotic cardiovascular disease (ASCVD).
“There’s an injectable version of this that’s been available for several years,” says Dr. Wahaj Aman, MD, a cardiologist with Memorial Hermann & UTHealth Houston. “However, there was no oral version. This is a game changer.”
According to clinical trials, Lipfendra is well-tolerated and effective for adults who have hypercholesterolemia (high levels of cholesterol in the blood), including those with heterozygous familial hypercholesterolemia (HeFH), an inherited form of high cholesterol.
How does Lipfendra work?
To understand how Lipfendra works, you need to understand what PCSK9 is and how it affects LDL cholesterol.
“There are LDL receptors on the liver that remove the plaque-forming LDL from our bloodstream,” explains Frank Wilklow, MD, cardiology specialist at LCMC Health in New Orleans. “The duration and longevity of those receptors is determined by a protein called PCSK9.” PCSK9 binds to LDL receptors on liver cells and breaks them down. This is problematic because LDL receptors help remove LDL from the bloodstream.
“Lipfendra is a macrocyclic peptide that blocks the effect of PCSK9, making our LDL receptors last longer and remove more of the harmful LDL from our bloodstream,” says Dr. Wilklow. In other words, it helps your liver get rid of more bad cholesterol.
Statins, on the other hand, lower cholesterol mainly by reducing the production of cholesterol in the liver. They do this by blocking HMG-CoA reductase enzymes, which your body uses to produce cholesterol.
Who is Lipfendra for?
Lipfendra is FDA approved for adults with hypercholesterolemia, including those with inherited high cholesterol and those who need additional help reducing LDL cholesterol. It is indicated to be used alongside lifestyle changes such as eating a heart-healthy diet and exercise.
Several groups of people may benefit from taking Lipfendra, including those who:
- Need additional help lowering LDL beyond what other medications, like statins, can provide
- Have statin intolerance or cannot handle the side effects of statins
- Have a genetic form of high cholesterol
Lipfendra may be used in patients who take statins and still need an LDL-lowering medication on board, Dr. Aman explains.
“A lot of people, for example, take 40 milligrams of atorvastatin, and their LDL is still not at goal, which for people who have had heart attacks and strokes is around 55 or lower,” says Dr. Aman. “This is where Lipfendra comes in.”
To determine if Lipfendra is a good option for a patient, healthcare providers evaluate cholesterol levels, cardiovascular risk, and other medications the person may be taking.
How do you take Lipfendra?
The recommended dosage of Lipfendra is 20 mg once a day, taken in the morning on an empty stomach. Swallow the tablet whole. Don’t crush, chew, or split the tablet.
“After taking the medication, wait at least 30 minutes before eating or drinking anything besides water because food will reduce the medication’s absorption,” explains Erika Gray, Pharm.D., founder and chief medical officer at ToolBox Genomics. “The medication does not need to be refrigerated or titrated.”
Per the label, black coffee and plain tea are also okay during that 30-minute window. Keep the tablets in their original bottle with the desiccant to protect them from moisture.
If you happen to miss a dose, take it as soon as you remember, as long as it is at least 30 minutes before your next meal. Don’t take two doses in the same day. If you aren’t sure of what to do if you miss a dose, or if you have questions, consult your healthcare provider or pharmacist.
What are the side effects of Lipfendra?
The CORALreef Lipids trial in adults with hypercholesterolemia found the safety profile of the drug similar to placebo (an inactive substance, or “fake” drug). In the CORALreef HeFH trial, two side effects were more common with the drug:
- Diarrhea: 7% with Lipfendra versus 2% with placebo
- Dizziness: 9% with Lipfendra versus 4% with placebo
If you experience severe adverse reactions, including allergic reactions like hives, difficulty breathing, or swelling, seek emergency medical treatment immediately.
Are there other risks or warnings to know about?
There are currently no contraindications listed on the drug label. However, it’s not approved for children, since there are no data on its safety and effectiveness in those under 18. In addition, there’s limited info on its use in pregnancy or breastfeeding. “The medication should not be used in pediatrics,” Dr. Gray warns. “Breastfeeding mothers should also avoid the medication because safety is unknown.”
Keep in mind that Lipfendra is a very new cholesterol medication. While the medication lowers LDL, researchers are still determining whether the medication can reduce cardiovascular events like strokes and heart attacks. A phase 3 clinical trial evaluating its efficacy, known as CORALreef Outcomes, is expected to have preliminary findings in 2029.
This doesn’t mean that Lipfendra is without benefits; it simply means that it doesn’t have as much real-world history as statins. Before starting this drug or any medication, talk to your provider about all medications you’re taking as well as your full health history.
Lipfendra vs. statins: What’s the difference?
While both Lipfendra and statins lower LDL cholesterol, they differ in exactly how they do that. Lipfendra blocks PCSK9, and statins reduce cholesterol production in the liver.
The two types of medications aren’t alternatives; in fact, they can actually work together.
In the CORALreef Lipids trial, Lipfendra lowered LDL by around 57% at 24 weeks. Most patients in that trial were already taking a statin, so that number is on top of statin therapy. Statins alone lower LDL by 30% to 49% at moderate intensity and by 50% or more at high intensity.
The data is promising for people who take statins but aren’t at their LDL goal. “Patients who cannot tolerate statins due to side effects, such as muscle aches or liver enzyme elevation, would also benefit from Lipfendra,” Dr. Wilklow adds. Since most patients in the trials were on statins, however, more data is needed on the use of Lipfendra without a statin.
How much does Lipfendra cost?
While the amount you pay for Lipfendra may vary due to a number of factors, a typical retail price for those paying out of pocket is around $400 for 30, 20 mg tablets. If you use a SingleCare coupon, however, the price can be as low as $310 for the same prescription. Since Lipfendra is a new drug, insurance coverage is still rolling out.
Frequently asked questions
Is Lipfendra the same as a statin?
No, Lipfendra is not the same as a statin because it lowers LDL cholesterol by inhibiting PCSK9, whereas a statin reduces the production of LDL cholesterol in the liver. Because they operate differently, the medications may be taken together under the guidance of a provider.
Who is a good candidate for Lipfendra?
Lipfendra is approved for adults with hypercholesterolemia, as they may need more support than a statin to reduce LDL cholesterol. A provider will evaluate your medical history, current medications, and cholesterol levels to determine if you’re a good candidate for the drug.
Is Lipfendra covered by insurance?
Some insurance providers and plans cover Lipfendra. However, because the drug is so new to the market, there may be prior authorization requirements and coverage restrictions.
The SingleCare prices in this article are the most accurate at the time of publishing in ZIP code 23666 as of Oct. 15, 2026. Prices vary by pharmacy. Visit our coupon page for updated drug prices at pharmacies near you.
- Lipfendra (enlicitide) prescribing information, U.S. Food and Drug Administration (2026)
- Label: Lipfendra tablet, film coated, DailyMed (2026)
- FDA approves first oral therapy that inhibits PCSK9 to lower bad cholesterol in adults with high cholesterol, U.S. Food and Drug Administration (2026)
- Merck’s LIPFENDRA (enlicitide) is the first and only once-daily oral PCSK9 inhibitor approved by the U.S. FDA to reduce LDL-C in adults with hypercholesterolemia, Merck (2026)
- A placebo-controlled trial of the oral PCSK9 inhibitor enlicitide, The New England Journal of Medicine (2026)
- CORALreef Lipids: Oral PCSK9 inhibitor enlicitide reduces LDL-C in high-risk patients, American College of Cardiology (2026)
- Efficacy and safety of oral PCSK9 inhibitor enlicitide in adults with heterozygous familial hypercholesterolemia: A randomized clinical trial, JAMA (2026)
- A study of enlicitide decanoate (MK-0616 oral PCSK9 inhibitor) in adults with hypercholesterolemia (MK-0616-013) CORALreef Lipids, National Library of Medicine (2026)
- Outcomes study: CORALreef Outcomes, Merck Clinical Trials (accessed 2026)
- ACC/AHA issue updated guideline for managing lipids, cholesterol, American College of Cardiology (2026)
- Statin medications, StatPearls (2024)
Featured experts
- Wahaj Aman, MD, an interventional cardiologist with Memorial Hermann and UTHealth Houston.
- Frank Wilklow, MD, an interventional cardiologist at LCMC Health in New Orleans.
- Erika Gray, Pharm.D., co-founder and chief medical officer at Genestyle.
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