Enlicitide pill reduces LDL cholesterol by 60% in phase 3 trial

An experimental oral pill called enlicitide lowered LDL cholesterol by about 60% in a large phase three clinical trial, according to results published in The New England Journal of Medicine. The trial, led by Dr. Ann Marie Navar at UT Southwestern Medical Center and sponsored by Merck, involved 2,909 participants mostly already on statins. If approved, the daily pill could improve access to effective cholesterol treatment.

The phase three trial tested enlicitide, an oral PCSK9 inhibitor, against a placebo in 2,909 participants with atherosclerosis or at risk due to related conditions. Most were taking statins, with average LDL levels at 96 mg/dl, above targets of 70 mg/dl for those with atherosclerosis and 55 mg/dl for at-risk individuals. After 24 weeks, enlicitide reduced LDL by about 60% compared to placebo, with benefits sustained over a year. It also lowered non-HDL cholesterol, apolipoprotein B, and lipoprotein(a).

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Illustration of scientists analyzing genetic data linking lower cholesterol to reduced dementia risk in a lab setting.
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Genetic study links lower cholesterol to reduced dementia risk

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A large-scale genetic analysis of about 1.09 million people suggests that lifelong, genetically lower cholesterol—specifically non‑HDL cholesterol—is associated with substantially reduced dementia risk. Using Mendelian randomization to emulate the effects of cholesterol‑lowering drug targets such as those for statins (HMGCR) and ezetimibe (NPC1L1), the study found up to an approximately 80% lower risk per 1 mmol/L reduction for some targets. ([research-information.bris.ac.uk](https://research-information.bris.ac.uk/en/publications/cholesterollowering-drug-targets-reduce-risk-of-dementia-mendelia?utm_source=openai))

Researchers from Mass General Brigham found that the cholesterol drug evolocumab cuts the risk of first-time major cardiovascular events by 31% in high-risk patients with diabetes who lack diagnosed atherosclerosis. The results, from a subgroup analysis of the VESALIUS-CV trial, were presented at the American College of Cardiology's Annual Scientific Session and published in JAMA. Patients on the drug saw LDL cholesterol levels drop significantly alongside standard treatments.

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The American College of Cardiology and American Heart Association have issued new guidelines on cholesterol screening and management, urging earlier testing and personalized risk assessments. The recommendations, presented on March 28 in New Orleans, emphasize lowering LDL cholesterol and incorporating genetic factors like lipoprotein(a). A new risk calculator aims to predict heart disease over longer periods.

A prespecified analysis of the SELECT trial reports that weekly semaglutide lowered the risk of heart attacks and strokes by about 20% in adults with established cardiovascular disease and overweight or obesity—even when little weight was lost—suggesting benefits beyond slimming alone.

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Researchers at Tohoku University report that lubiprostone, a medication commonly used to treat chronic constipation, helped slow the decline of kidney function in patients with chronic kidney disease in a Phase II trial. The findings emerged from work exploring how gut health and constipation influence kidney outcomes.

Researchers led by Mass General Brigham and the Technical University of Munich report that tirzepatide and semaglutide are associated with significant reductions in heart attacks, strokes and death among adults with type 2 diabetes at elevated cardiovascular risk. Drawing on nearly one million insurance records, the Nature Medicine analysis finds strong and early heart protection from both GLP‑1–based drugs, with only modest differences between them.

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Researchers at Karolinska Institutet and Stockholm University have developed an experimental oral drug that boosts metabolism in skeletal muscle, improving blood sugar control and fat burning in early studies without reducing appetite or muscle mass. Unlike GLP-1-based drugs such as Ozempic, the candidate acts directly on muscle tissue and has shown good tolerability in an initial clinical trial, according to the study authors.

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