On the horizon: A pill that could transform cholesterol management

A promising daily oral therapy that dramatically reduces low-density lipoprotein cholesterol (LDL-C)—the “bad” cholesterol linked to heart attacks and strokes—has captured global attention after strong results from a late-stage clinical trial. The drug, enlicitide, developed by Merck, lowered LDL-C by 58.2 percent in adults with a genetic form of high cholesterol, according to findings recently published in the Journal of the American Medical Association (JAMA). The prospect of achieving such reductions with a simple pill, rather than an injection, has generated significant excitement among cardiologists seeking more patient-friendly treatment options.
The phase 3 study, led by researchers at the Texas Heart Institute, enroled 303 adults across 59 medical sites in 17 countries.
All participants were diagnosed with heterozygous familial hypercholesterolaemia (HeFH), a hereditary condition that elevates LDL levels and significantly increases the risk of premature cardiovascular disease.
In India, where heart disease remains a leading cause of mortality, the potential impact of a potent and easy-to-use cholesterol-lowering drug could be enormous.
Evidence suggests that India is facing an unprecedented lipid burden. A large survey by the Indian Council of Medical Research (ICMR) and the Madras Diabetes Research Foundation, published in The Lancet in 2023, reported that more than 81 percent of Indians have dyslipidaemia, while 20.9 percent—about 185 million people—have elevated LDL-C levels.
In response to this growing challenge, the Cardiological Society of India’s first-ever lipid management guidelines, released in July 2024, recommend that high-risk individuals such as those with diabetes or hypertension maintain LDL-C levels below 70 mg/dL.
Despite the widespread use of statins—the backbone of cholesterol management—around 20 percent of patients fail to reach target LDL levels even with treatment.
Others cannot tolerate statins due to side effects such as muscle pain or weakness. For this subset of patients, additional therapies are essential.
Enlicitide belongs to the same class of drugs as injectables such as evolocumab and inclisiran, both of which are available in India as third-line therapies for cholesterol management.
Like them, enlicitide targets PCSK9, an enzyme that reduces the liver’s ability to clear LDL cholesterol from the bloodstream. By silencing the gene responsible for PCSK9 production, the therapy enhances the liver’s natural LDL-removal mechanism.
While the trial results are promising, experts caution that the study measured cholesterol reduction but did not evaluate whether enlicitide prevents heart attacks, strokes, or cardiovascular deaths—key outcomes needed before widespread adoption.