#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention

Mar 16, 2026 52m 40s 3 insights Episode Page ↗
Peter Attia discusses obicetrapib, an investigational CETP inhibitor, exploring its history, how it lowers LDL and Lp(a), and its potential cardiovascular benefits. He also delves into emerging data suggesting implications for Alzheimer's disease, particularly in APOE4 carriers, based on biomarker changes.
Actionable Insights

1. Re-evaluate High HDL Cholesterol

Do not assume high HDL cholesterol levels guarantee cardiovascular safety, as Mendelian randomizations have not supported a causal link between high HDL and reduced cardiovascular disease outcomes. This challenges the common notion that high HDL is always ‘good cholesterol’.

2. Screen for SRB1 Mutations

If you have consistently very high HDL cholesterol (e.g., 110-120 mg/dL) and low LDL cholesterol, consider getting a calcium score. This can help rule out a loss-of-function SRB1 mutation, which can lead to high HDL but paradoxically increased coronary artery disease risk.

3. APOE4 Not Deterministic

While carrying one or two copies of the APOE4 gene increases the risk for Alzheimer’s disease, it is not deterministic. Many individuals with APOE4 genes live to advanced age without cognitive decline, indicating that other factors can significantly modify this genetic risk.