#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention
3/16/202653 min
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
Transcript preview
First 90 secondsPeter Attia· Host0:00
[upbeat music] Hey everyone. Welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe. 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 obeticholic acid. 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