What if a simple daily pill could cut your "bad" cholesterol level by more than half? That is the spectacular promise of enlicitide, an experimental drug developed by Merck whose clinical results, published in the New England Journal of Medicine in early 2026, have sent shockwaves through the world of cardiology.

What exactly is enlicitide?

Enlicitide (or enlicitide decanoate) is an oral inhibitor of the PCSK9 protein. To understand how it works, it is worth going back to basics: PCSK9 is a protein naturally present in our body that prevents the liver from efficiently eliminating LDL cholesterol from the blood. By blocking this protein, enlicitide allows the liver to better "clean up" circulating cholesterol.

Until now, PCSK9 inhibitors already existed in the form of injections (such as evolocumab or alirocumab), administered every two to four weeks. Effective, certainly, but burdensome for patients. Enlicitide radically changes the game: it is a simple pill taken once a day, orally. A revolution in terms of convenience and accessibility.

Impressive clinical results

The phase 3 clinical trial, called CORALreef, enrolled nearly 2,900 patients with atherosclerosis or significant cardiovascular risk factors. Two-thirds of participants received enlicitide, while the remaining third received a placebo.

The results after 24 weeks are unambiguous: patients on enlicitide saw their LDL cholesterol drop by approximately 60% compared to the placebo group. But that is not all. The drug also significantly reduced other lipid markers associated with cardiovascular disease, including non-HDL cholesterol, apolipoprotein B, and lipoprotein(a). These results were maintained stably over a one-year follow-up period.

"These LDL cholesterol reductions are the largest ever achieved with an oral medication since the development of statins."
— Dr. Ann Marie Navar, UT Southwestern Medical Center

Why this is a major breakthrough

Elevated LDL cholesterol remains one of the main risk factors for cardiovascular disease, the leading cause of death worldwide. Statins, prescribed for decades, constitute the standard treatment. However, many patients do not reach their cholesterol targets even at maximum statin doses.

Enlicitide fills a considerable therapeutic gap. Unlike existing PCSK9 injections, which pose problems of adherence, cost, and accessibility, this oral pill could be prescribed much more widely. As Dr. Navar notes: "An oral treatment as effective as enlicitide has the potential to substantially improve our ability to prevent heart attacks and strokes at a population level."

What about statins?

Enlicitide does not replace statins, but complements them. In the CORALreef trial, most participants were already taking statins at maximum dose. Enlicitide was added to the existing treatment to achieve an additional and substantial reduction in LDL cholesterol. For patients who do not tolerate statins — estimated at 5 to 10% of those treated — enlicitide could also represent an excellent alternative.

When will it be available?

The US FDA is currently reviewing the enlicitide file, with an accelerated approval process thanks to the award of a National Priority Voucher. A complementary trial is underway to determine whether the reduction in LDL cholesterol effectively translates into a reduction in heart attacks and strokes, which would constitute the ultimate proof of its clinical benefit.

In Europe, regulatory procedures will likely follow with a slight delay. But given the scale of the results, European cardiologists are following this case with evident interest. If all goes well, enlicitide could be available as early as the end of 2026 or during 2027 in several countries.

Key takeaways

Enlicitide potentially represents the greatest advance in cholesterol treatment since the arrival of statins more than thirty years ago. A daily pill capable of reducing bad cholesterol by 60%, with an encouraging tolerability profile and incomparable ease of use compared to existing injections: the world of preventive cardiology could well be experiencing a historic turning point.

It remains to be confirmed that this impressive reduction in cholesterol actually translates into saved lives. The upcoming clinical trial results will be decisive. In the meantime, one thing is certain: the hope for a powerful oral treatment against cholesterol has never been more concrete.