Experimental cholesterol-lowering pill may offer new option for millions

A new experimental pill has shown remarkable promise in reducing harmful cholesterol levels for patients who remain at high risk of heart attacks despite taking statins, according to research published Wednesday in the New England Journal of Medicine.

The medication, named enlicitide, reduced LDL or “bad” cholesterol by as much as 60% over a six-month period in high-risk patients. This significant reduction offers hope to millions who struggle to reach recommended cholesterol targets with existing treatments.

“None come close to the degree of LDL cholesterol lowering that we see with enlicitide,” said study lead author Dr. Ann Marie Navar, a cardiologist at UT Southwestern Medical Center, comparing the new pill to other statin add-on treatments currently available.

Heart disease remains the leading cause of death in the United States, with elevated LDL cholesterol—which causes plaque buildup in arteries—being a primary risk factor for heart attacks and strokes. Medical guidelines recommend that people with heart disease or high cholesterol maintain LDL levels below 70, or even lower for those at very high risk.

While statins like Lipitor and Crestor (or their generic equivalents) effectively reduce cholesterol by blocking the liver’s production of the substance, many patients need additional therapy to reach their target levels. Currently, the most powerful additional treatments are injectable medications known as PCSK9 inhibitors, which work by blocking a liver protein that limits the body’s natural ability to clear cholesterol from the bloodstream.

Despite their effectiveness, these injectable treatments face significant adoption barriers. Many eligible patients avoid them due to the inconvenience of self-injection, complexity of prescribing, and historically high costs, though prices have decreased recently.

Enlicitide works through the same biological mechanism as these injectable drugs but in pill form—potentially offering a more convenient alternative that could dramatically increase treatment accessibility. The medication must be taken on an empty stomach to achieve optimal results.

“The research offers compelling evidence that the new pill lowers cholesterol about as much as those PCSK9 shots,” wrote Dr. William Boden of Boston University and the VA New England Healthcare System in an accompanying editorial. Boden, who wasn’t involved in the research, noted the potential significance of this development for clinical practice.

The study, funded by pharmaceutical company Merck, involved more than 2,900 high-risk patients who were randomly assigned to add either daily enlicitide or a placebo to their standard treatment regimen. The cholesterol-lowering benefit persisted throughout the one-year study period, with only a slight decrease in effectiveness over time. Importantly, researchers found no significant safety differences between the treatment and placebo groups.

Merck plans to use this data as part of its application for FDA approval. The agency has already added enlicitide to its program for expedited review, signaling potential recognition of the medication’s clinical importance.

However, researchers caution that while the cholesterol reduction is impressive, longer-term studies are still needed to confirm whether this translates to actual reductions in heart attacks, strokes, and deaths. A larger trial involving more than 14,000 patients is currently underway to answer this crucial question.

If approved, enlicitide would represent a significant advance in cardiovascular medicine, potentially helping millions of Americans who struggle to achieve optimal cholesterol levels with current therapies. The pill format could overcome many of the barriers that have limited the use of injectable PCSK9 inhibitors, making this powerful approach to cholesterol management more accessible to the broader population of high-risk patients.