NEW YORK CITY — For some people with high cholesterol, making lifestyle changes and taking routine statin medications may not be sufficient to help them reach their target cholesterol levels. For these patients, a new experimental pill could offer some hope.
Phase 3 trial data found that people who took the investigational drug enlicitide with their routine cholesterol-lowering regimen, like statins, saw up to a 60% reduction in their LDL or “bad” cholesterol after 24 weeks of daily treatment, according to a news release about the results. That was in comparison with people who took a placebo along with their routine cholesterol-lowering medications. All study participants had high levels of LDL cholesterol and a history of either a major cardiovascular disease event, or they were at an increased risk for one.
The new results, which have not yet been published in a peer-reviewed journal, were presented Saturday at the American Heart Association’s Scientific Sessions.
Having high cholesterol in the blood can lead to a buildup called “plaque” on the walls of the arteries, raising the risk of cardiovascular disease. Heart disease is the leading cause of death in the United States. It’s estimated that one person dies every 34 seconds from cardiovascular disease in the U.S.
Merck, the pharmaceutical company behind enlicitide, plans to apply for Food and Drug Administration approval of enlicitide early next year, said Dr. Puja Banka, the company’s associate vice president of clinical research and global clinical development.
“We wanted to show what enlicitide can deliver on top of statins, because we know that 70% of patients that are treated with lipid-lowering therapies still don’t reach their guideline-directed goals,” Banka said about the new data. “So, the idea is really to show what we can achieve with enlicitide on top of statins.”
When statins alone are not enough
The new Phase 3 trial included 2,912 adults, with an average age of 63, who either had a previous heart attack or stroke or were at intermediate or high risk of a heart attack or stroke within the next 10 years. Data were collected across 14 countries between August 2023 and July 2025.
All of the adults in the study had elevated LDL cholesterol levels despite being on a stable course of lipid-lowering therapy like statins for 30 days or more. About 97% of them were taking statins and 26% were also taking another type of medication to help lower cholesterol levels – and they all continued these therapies during the study.
But as an additional treatment, some of the adults were administered a once-daily pill of enlicitide and others were given a placebo.
Enlicitide is a type of cholesterol-lowering drug known as a PCSK9 inhibitor, which works by helping to clear “bad” LDL cholesterol out of the bloodstream. On the other hand, statins lower LDL cholesterol by blocking an enzyme in the liver, which then forces the liver to remove more LDL cholesterol from the body.
“Thus, it might be expected that adding enlicitide that works by a different mechanism to statins could further reduce LDL cholesterol,” Dr. Kristin Newby, a cardiologist and professor at Duke University School of Medicine, who was not involved in the study, said in an email.
The researchers found that after 24 weeks, the adults taking enlicitide not only saw up to a 60% reduction in LDL cholesterol, but reductions were sustained through 52 weeks.
The adults taking enlicitide also showed a 53% reduction in a combination of all other cholesterol except for “good” HDL cholesterol; a 50% decrease in ApoB, a protein that helps carry fat and various “bad” types of cholesterol throughout the body; and a 28% drop in a type of fat in the body known as lipoprotein(a).
As for the safety of the drug, about 10% of the adults taking enlicitide experienced serious adverse events during the study and a similar share, about 12%, of those taking a placebo experienced adverse events in the study.
“Ultimately, the side effects were balanced between the enlicitide arm and the placebo arm,” Banka said. “There wasn’t a particular adverse event that stands out as imbalanced between the two.”
Some of the adverse events reported in the trial were gastrointestinal disorders and certain infections, but the occurrence of these events was similar across both groups.
“This provides some reasonable assurance of no major or high frequency adverse events or side effects,” said Newby, who is an expert with the American Heart Association.
“However, similar to other new therapeutics, larger outcomes studies and post-marketing surveillance will be needed to identify any low frequency adverse effects that might occur,” Newby said. “The major benefit that is clear from this study is that enlicitide is very efficacious at lowering LDL cholesterol (by about 55%) compared with placebo on a background of statin therapy, and secondarily, it helps more people reach their LDL cholesterol treatment goal than with statins alone.”
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