Peps
What PCSK9 does
The liver clears LDL ("bad") cholesterol from the blood using LDL receptors on its cells. After each round trip, a receptor normally returns to the cell surface to catch more LDL. PCSK9 is a protein that tags those receptors for destruction instead, so fewer remain and more LDL stays in circulation.
Blocking PCSK9 lets the receptors keep recycling, and LDL levels drop sharply, typically by about half or more on top of a statin. Four approved medicines now do this in three different ways.
The antibodies: Repatha and Praluent
Repatha (evolocumab, from Amgen) and Praluent (alirocumab, from Sanofi and Regeneron) are monoclonal antibodies: large proteins, dozens of times bigger than a typical peptide, made in engineered cell cultures. Each grabs PCSK9 in the blood. Because they are proteins, they would be digested if swallowed, so they are injected under the skin every two or four weeks.
Both have large outcome trials. In FOURIER, 27,564 people with heart or blood-vessel disease who were already on a statin received evolocumab or placebo. LDL fell 59%, and over a median 2.2 years the combined rate of cardiovascular death, heart attack or stroke fell from 7.4% to 5.9%. In ODYSSEY OUTCOMES, 18,924 people who had recently had an acute coronary syndrome received alirocumab or placebo; major cardiovascular events fell from 11.1% to 9.5% over a median 2.8 years.
In 2025, VESALIUS-CV extended the evolocumab evidence to 12,257 people with atherosclerosis or diabetes who had never had a heart attack or stroke. Over a median 4.6 years, the first such events fell from an estimated 8.0% to 6.2%. In these trials, injection-site reactions were the main side effect that was more common than with placebo.
Source: BioLongevity source document directory ↗
The gene silencer: Leqvio
Leqvio (inclisiran, from Novartis) is neither an antibody nor a peptide. It is a small interfering RNA (siRNA) that is taken up by liver cells and switches off the instructions for making PCSK9, so less of the protein is produced in the first place. Its effect lasts months, so after two starting doses it is injected twice a year.
In the ORION-10 and ORION-11 trials (about 3,200 people combined), inclisiran lowered LDL by roughly 50% compared with placebo over 18 months. Injection-site reactions were more frequent than with placebo but generally mild. Its outcome trials, which test whether it reduces heart attacks and strokes, had not reported when this guide was checked; results are expected in 2027.
The peptide: enlicitide, the first PCSK9 pill
Enlicitide (Merck, brand name Lipfendra) is the peptide in this group. It is a macrocyclic, or ring-shaped, peptide built to bind PCSK9 tightly and to survive the digestive tract well enough to work as a once-daily tablet. Ordinary peptides are broken down when swallowed, which is why most peptide medicines are injected.
In the phase 3 CORALreef Lipids trial, 2,909 adults with or at risk of atherosclerotic disease took enlicitide or placebo for a year. LDL fell about 57% with enlicitide versus a 3% rise with placebo at 24 weeks, and adverse events were similar between groups. The FDA approved it in July 2026 to lower LDL cholesterol. Unlike Repatha and Praluent, it has not yet been shown to reduce heart attacks or strokes; that outcomes trial is still running.
Source: A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide ↗
How they compare
Same target, different tools: the antibodies neutralize PCSK9 already in the blood, the siRNA stops the liver making it, and the peptide blocks it with a compact ring-shaped molecule that can be swallowed. The practical differences are how they are taken (injections every few weeks, twice-yearly injections, or a daily pill) and how much evidence each has. Only the antibodies have completed trials showing fewer heart attacks and strokes so far.
Choosing between them, or whether any is appropriate, depends on a person's cholesterol, risk, other medicines and insurance coverage, and is a decision for a clinician. All four are prescription medicines. None is sold as a research peptide, and nothing sold by research-chemical sellers is a substitute for them.
Source: BioLongevity source document directory ↗
Source: BioLongevity source document directory ↗
Source: A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide ↗
Continue with the original research
Study examples are based on selected publication abstracts and the explicitly described source documents. This is not a systematic review or an individualized treatment guide. Editorial scope and methods.