On July 16, 2026, the Food and Drug Administration (FDA) approved Lipfendra (enlicitide), the first ever oral PCSK9 inhibitor, for the treatment of high cholesterol (hypercholesterolemia) and heterozygous familial hypercholesterolemia.
Lipfendra comes in pill form, and should be taken daily in 20 milligram (mg) doses. It works by reducing blood levels of low-density lipoprotein (LDL) cholesterol, or “bad cholesterol.”
But how does this new treatment compare to statins, some of the most commonly used cholesterol-lowering drugs, and who is it the right choice for?
To answer these, and other salient questions, Medical News Today reached out to Rigved Tadwalkar, MD, FACC, a consultative cardiologist, and director of the Digital Transformation Pacific Heart Institute in Santa Monica, CA.
Most people may be familiar with statins, a type of cholesterol-lowering drugs taken by millions of people in the United States.
They work by essentially “tell[ing] the liver to make less cholesterol by blocking an enzyme called HMG-CoA reductase,” which is involved in cholesterol synthesis, Tadwalkar explained.
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By contrast, Lipfendra “blocks PCSK9, a protein that causes the liver’s LDL receptors to be broken down,” he detailed.
“With more of those receptors available, the liver can pull more LDL cholesterol out of the bloodstream. We already know this mechanism from injectable PCSK9 treatments such as evolocumab and alirocumab. Lipfendra targets the same biological pathway, but delivers it in a once-daily pill rather than an injection.”
– Rigved Tadwalkar, MD, FACC
“It can be,” said Tadwalkar, “depending on what you are comparing.”
“In the pivotal trials, Lipfendra lowered LDL cholesterol by about 56 to 59% compared with placebo, mostly in patients who were already taking statins. High-intensity statins generally lower LDL cholesterol by at least 50%, while moderate-intensity statins typically lower it by 30 to 49%,” he told us.
Despite these encouraging results, the cardiologist cautioned that “Lipfendra was not tested head-to-head against a statin, so it would be misleading to simply call one better than the other.”
He also pointed our that: “Statins have decades of cardiovascular outcomes data behind them. Lipfendra has shown powerful LDL lowering [effects], while its own trial looking at heart attacks, strokes and other cardiovascular outcomes is still underway.”
In Tadwalkar’s view, the new LDL cholesterol lowering pill might bring the most benefits not on its own but “as an additional option when a statin is not getting the LDL cholesterol low enough, or when the maximally tolerated statin dose is limited.”
On that note, Tadwalkar emphasized tha Lipfendra can “absolutely” be taken alongside other cholesterol-lowering medications when needed. In fact, he pointed out, “that is how [the drug] was largely studied.”
“Most participants [in the Lipfendra clinical trials] were already taking moderate- or high-intensity statin therapy, sometimes along with another cholesterol medication. Lipfendra could therefore be used with a statin, ezetimibe or another treatment when a patient needs more LDL lowering. It would still be used alongside a heart-healthy diet and regular exercise, not as a substitute for them.”
— Rigved Tadwalkar, MD, FACC
However, he noted, “I would not expect Lipfendra to be combined with an injectable PCSK9 inhibitor.”
“Since they target the same pathway, there is no established benefit to using them together, and patients taking another PCSK9 inhibitor were excluded from the pivotal trial,” said the cardiologist.
In terms of who might want to consider whether Lipfendra is an appropriate treatment for them, and discuss that option with their healthcare prodvider, Tadwalkar advised that “the most obvious group is adults whose LDL cholesterol remains above an appropriate level despite their maximally tolerated statin.”
This might mean different things for different people, he clarified: “For some people, the maximally tolerated dose is a high-intensity statin. For others, it is a lower dose, and for a smaller group it may be no statin at all after a thoughtful evaluation of prior symptoms and treatment attempts.”
“The conversation may be especially relevant for people who already have atherosclerotic cardiovascular disease, those at high risk of developing it, and people with a genetic form of high cholesterol called heterozygous familial hypercholesterolemia,” said Tadwalkar.
Lipfendra may also be an appropriate alternative for those who would benefit from an injectable PCSK9 inhibitor but who would rather avoid this more invasive treatment, he added.
Lipfendra could help a lot of people keep their cholesterol in check but it is definitely — at least for the time being — not an option for minors, said Tadwalkar.
“The FDA label does not list any formal contraindications, but Lipfendra is approved only for adults, so its safety and effectiveness have not been established in children,” he pointed out.
“Pregnancy also deserves special attention,” he emphasized. “The prescribing information advises stopping it when pregnancy is recognized unless the expected benefit is judged to outweigh the potential risk.”
There is also something to be said about the very specific regimen this new treatment requires, and whether or not it may make it difficult to adhere to.
Tadwalkar explained:
“The morning routine is important and may make the medication a poor fit for some people. It has to be taken on an empty stomach with water, black coffee or plain tea. The tablet must be swallowed whole, and the patient then needs to wait at least 30 minutes before eating or drinking anything else. That may sound like a small detail, but with a daily medicine, small details can determine whether someone actually takes it consistently.”
Thus, he added, “for some patients, an established injectable PCSK9 inhibitor, typically given once every 2 weeks, may be a better fit.”
Unlike Lipfendra, injectable PCSK9 inhibitors do “have proven cardiovascular outcomes data, along with imaging evidence showing coronary plaque regression and more favorable plaque characteristics,” the cardiologist noted.
Finally, he noted, people should not be tempted to switch to a different medication just because it’s newer. If you are “already at an appropriate LDL level on a well-tolerated regimen,” it may be best to stick to the known and proven approach, said Tadwalkar.
