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

#384 - 特别篇 —— Obicetrapib：具有心血管益处和潜在预防阿尔茨海默病的CETP抑制剂

The Peter Attia Drive

2026-03-16

52 分钟
PDF

单集简介 ...

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this special episode, Peter takes a deep dive into obicetrapib, an investigational drug that has captured his attention and renewed interest in an entire class of therapies known as CETP inhibitors. He explains what obicetrapib is and how it works, revisits the history of CETP inhibitors and why earlier versions of these drugs failed—sometimes dramatically—and breaks down the key clinical trials designed to evaluate their impact on cardiovascular risk. Peter examines how obicetrapib influences major lipid biomarkers, including LDL cholesterol and lipoprotein(a) [Lp(a)], and discusses emerging evidence from a study that explored the drug's effects on Alzheimer's-related blood biomarkers. He also highlights intriguing findings in individuals carrying the APOE4 allele and reflects on what these early results may mean for both cardiovascular disease prevention and potential implications for Alzheimer's risk, as well as how he is thinking about this therapy in the context of caring for his own patients. We discuss: Introducing obicetrapib: CETP inhibitor history, lipid biology, and early Alzheimer's biomarker signals in APOE4 carriers [2:15]; CETP biology explained: lipoproteins, reverse cholesterol transport, and how CETP inhibition alters HDL and LDL particles [5:15]; The early CETP inhibitor story: why raising HDL cholesterol alone failed to deliver cardiovascular protection [13:45]; The rise and fall of early CETP inhibitors: torcetrapib, dalcetrapib, evacetrapib, and anacetrapib [18:30]; Why obicetrapib may succeed where earlier CETP inhibitors failed [23:30]; The BROADWAY trial: obicetrapib's effects on LDL, ApoB, Lp(a), and residual cardiovascular risk [26:00]; Brain lipid metabolism and APOE4: how CETP inhibition may influence cholesterol transport in Alzheimer's disease [30:45]; Findings from the substudy of the BROADWAY trial which looked at changes in biomarkers of Alzheimer's disease [40:00]; Interpreting the BROADWAY Alzheimer's biomarker results: limitations, cautious optimism, and the need for a dedicated prevention trial [46:45]; Why Peter is optimistic about obicetrapib: cardiovascular benefits, Lp(a) reduction, and the path toward approval [50:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
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单集文稿 ...

  • Hey, everyone.

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  • Welcome to a special episode of The Drive.

  • In this episode, I take a slightly different approach where I'm going to walk you through a single topic in depth, breaking down the science behind, in this case, a drug that caught my attention and has me very excited.

  • The drug is called Obacetrapib.

  • So I'm going to explain what it is, why it's generating renewed interest in cardiovascular medicine, at least as a class of drug, and why the emerging data may also have implications for Alzheimer's disease, particularly for those who carry an E4 allele.

  • So in this episode, I'm going to discuss what obocetripib is, how it works as a class of drug called a CETP inhibitor.

  • the history of these drugs and why the previous versions of them have failed, and in some cases spectacularly, the key clinical trials behind Obacetrapib and why they were designed, what they were designed to measure, the drug's effect on the major lipid biomarkers, including LpA, all very interesting, a study called the Broadway Biomarker Study and its findings in Alzheimer's-related blood biomarkers, again, including a very interesting subgroup in ApoE carriers.

  • And I guess most of all what these results mean, how do they have me thinking about this drug for my patients?

  • So without further delay, I hope you enjoy this special episode of The Drive.

  • So if you spend any time thinking about Alzheimer's disease research, you get pretty familiar with the emotional whiplash that accompanies it.

  • You know, one week you're going to see a biomarker.

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