A daily pill cut bad cholesterol by more than half in 24 weeks, trial finds

Statins, a common kind of cholesterol medicine, come as a pill. Another strong kind, which blocks a protein called PCSK9, has for years come only as a shot. Those shots are made of antibodies, large proteins that the gut would break down like food [1][3].

Now a trial of 2,909 adults has tested a pill that blocks the same protein. By week 24, bad cholesterol fell by 57.1 percent on average in people taking the pill. That is a little more than half. In people taking a look alike pill with no medicine in it, it rose by 3.0 percent [1].

One thing is worth saying early. The trial measured a blood test, not heart attacks or strokes, so it cannot say whether the pill prevents them. A separate trial is testing that, and it will not finish before late 2029 [1][4].

The pill is called enlicitide. The trial, known as CORALreef Lipids, was led by Ann Marie Navar of the University of Texas Southwestern Medical Center in Dallas. It was published in the New England Journal of Medicine in 2026. The drug company MSD, which makes the pill, paid for it [1].

Why does blocking this protein matter? LDL cholesterol, often called bad cholesterol, can build up inside blood vessels when there is too much of it in the blood. The liver pulls LDL out of the blood using small catchers on its cells, called receptors, which grab LDL as it passes. PCSK9 wears those catchers out sooner. With PCSK9 blocked, the catchers last longer, and the liver can clear more cholesterol [1].

The new pill is a peptide, a short chain of small building blocks called amino acids. The gut is built to break chains like that apart, which is why most peptide medicines are shots. This one is joined end to end into a ring, with many small chemical changes along it. Together they let enough of it get through the gut and into the blood [1][3].

The trial ran in many countries, and neither the people in it nor the researchers knew who got the real pill. Two kinds of adults could join: people who had already had a major heart or blood vessel problem, such as a heart attack, and people at risk of a first one. Chance decided who got what, with two people getting the real pill for every one who got the fake pill. Everyone took it daily for 52 weeks, which is one year. Their average age was 63, and about four in ten were women [1].

Some other blood fat measures that doctors keep track of also fell more on the real pill. The report says the rate of side effects did not seem to differ between the groups. The researchers summed up the trial this way [1]:

Among participants who had a history of or were at risk for a first atherosclerotic cardiovascular disease event, treatment with the oral PCSK9 inhibitor enlicitide resulted in significantly lower LDL cholesterol levels than placebo at 24 weeks.

Navar and colleagues, New England Journal of Medicine, 2026 [1]

In plain words, the pill lowered bad cholesterol much more than a fake pill did. That held in people with disease from fatty buildup in their blood vessels, or at risk of it. Notice what the sentence leaves out. It says nothing about heart attacks, because the trial did not count them [1].

How is a pill like this even made? A second paper, published in Science in 2026 by a team at Merck led by Artis Klapars, answers that. Building a ring shaped peptide with many changes used to take a long list of steps. The team used enzymes, proteins that speed up chemical work, to join the pieces and close the ring. They say this cut the number of steps by more than half [2].

Historically, many compelling therapeutic targets have been accessible only by injectable biologic drugs.

Klapars and colleagues, Science, 2026 [2]

In plain words, many useful targets in the body could only be reached by medicines given as shots. If rings like this one can be made in half the steps, more of those targets may be reached by a pill [2].

The pill has not fully beaten the gut, though. Its United States label says it is taken in the morning on an empty stomach, with water, black coffee or plain tea. Then at least 30 minutes must pass before any food or other drink. The ring buys the medicine enough time to get into the blood, but not unlimited time [3].

The label is also careful about heart attacks. It says that lowering LDL cut the risk of serious heart and blood vessel problems in trials of other medicines, statins and the antibody shots. It does not say this new pill has been shown to do that [3].

So what is still open? A trial of about 14,550 people at high risk of heart problems, listed as NCT06008756, is counting first heart and blood vessel problems. Its main results should be gathered by about November 2029 [4].

Until then, this work does not show that the pill prevents heart attacks or strokes. It also does not show how it compares with the antibody shots over many years. What it does show is narrower but still a first. A ring shaped peptide, swallowed once a day, lowered bad cholesterol by more than half in a trial that lasted a year [1][3][4].