Lipfendra

Lipfendra (enlicitide) is used to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH), along with diet and exercise. It is an oral tablet taken once a day that can be used alone or alongside a statin.

Lipfendra works by blocking a protein called PCSK9 (proprotein convertase subtilisin kexin type 9). Normally, PCSK9 attaches to LDL receptors on the surface of liver cells and causes them to break down. These receptors are what the liver uses to clear LDL cholesterol (the "bad" cholesterol) from the blood, so fewer receptors means more LDL cholesterol stays in circulation. By stopping PCSK9 from attaching to these receptors, Lipfendra leaves more of them available to remove LDL cholesterol, which lowers LDL cholesterol levels. Lipfendra belongs to the drug class called PCSK9 inhibitors.

Lipfendra (enlicitide) received FDA approval on July 16, 2026, and is the first oral PCSK9 inhibitor for lowering LDL-C to be approved. Approval was based on two Phase 3 trials from the CORALreef program.

• CORALreef Lipids (NCT05952856): LDL-C dropped 56% compared to placebo at week 24. After biologically impossible values were removed under revised data-handling rules, the reduction was 60% from the starting level (a post-hoc analysis).
• CORALreef HeFH (NCT05952869): in people with an inherited form of high cholesterol, LDL-C dropped 59% compared to placebo.

Both trials also showed reductions in non-HDL-C and ApoB. Safety in CORALreef Lipids was similar to placebo; in CORALreef HeFH, the most common side effects were diarrhea (7% vs 2%) and dizziness (9% vs 4%).

It is not known if Lipfendra is safe and effective in children.

• Take Lipfendra exactly as your healthcare provider tells you to.
• Take 1 tablet of Lipfendra by mouth each morning on an empty stomach with water, black coffee, or plain tea.
• Swallow the tablet whole. Do not split, crush or chew the tablet.
• After taking Lipfendra, wait at least 30 minutes before you eat or drink anything other than water, black coffee, or plain tea.
• You can take Lipfendra at the same time as you take your other medicines.
• If you miss a dose: Take it as soon as you remember, at least 30 minutes before the next food or drink (other than water, black coffee, or plain tea). Do not take 2 doses on the same day. Wait at least 30 minutes after taking the missed dose of Lipfendra before you eat or drink anything other than water, black coffee, or plain tea.
• If you take too much Lipfendra, call your healthcare provider or the Poison Help line (1-800-222-1222) or go to the nearest hospital emergency room right away. Advice is also available online at poisonhelp.org.

Before taking Lipfendra, tell your healthcare provider about all of your medical conditions, including if you:

• are pregnant or planning to become pregnant. It is not known if Lipfendra will harm your unborn baby. Tell your healthcare provider if you become pregnant while taking Lipfendra.
• are breastfeeding or plan to breastfeed. You and your healthcare provider should decide the best way to feed your baby if you take Lipfendra. You should not take Lipfendra and breastfeed without talking to your healthcare provider first.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Common side effects

In people with high cholesterol, the side effects of Lipfendra are about the same as in people who are not taking Lipfendra. In people with HeFH, the most common side effects of Lipfendra are diarrhea and dizziness.

These are not all the possible side effects of Lipfendra. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store Lipfendra at room temperature between 68°F and 77°F (20°C and 25°C).
• Store Lipfendra in the original package (pill bottle) with the lid tightly closed to protect from moisture.
• The Lipfendra bottle has a desiccant (something that absorbs moisture) to keep your medicine dry. Do not remove the desiccant from the bottle.

Keep Lipfendra and all medicines out of the reach of children.

Active ingredient: enlicitide decanoate

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium caprate. The tablet film coating contains calcium carbonate, ethylene glycol, and vinyl alcohol graft copolymer, glyceryl mono and dicaprylocaprate, polyvinyl alcohol, and talc. Carnauba wax is added as a polishing agent.

Lipfendra (enlicitide) is manufactured for Merck Sharp & Dohme LLC, Rahway, NJ 07065, USA.