The History of CETP Inhibitors: Four Drugs That Did Not Make It
Current as of November 2026
For more than twenty years, researchers studying cardiovascular medicine have tried to make a promising class of medications known as CETP inhibitors. The original goal of CETP inhibitors was to drastically increase “good” cholesterol, also known as high-density lipoprotein cholesterol (HDL-C), while at the same time lowering low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol. After decades of research and large clinical trials including tens of thousands of participants, CETP inhibitors are still being developed and studied to this day. There have been four major drug candidates in the CETP class which include torcetrapib, dalcetrapib, evacetrapib, and anacetrapib. However, each of these drugs were eventually discontinued or abandoned before reaching patients on the market. This blog tells the story of these four medications. It explains what happened in the trials, why each drug was stopped, and what twenty years of research taught doctors about lab tests versus actual heart risks.
What Is CETP, and What Does It Do?
Cholesteryl ester transfer protein (CETP) is a natural protein produced in your body, mainly in the liver. CETP travels throughout your blood and its main job is to pick up fats and cholesterol and move them between different packages in your bloodstream. To understand how CETP works, it is helpful to understand how cholesterol moves in your blood. Cholesterol is a waxy substance that cannot float or move in blood on its own. Cholesterol travels inside tiny packages made of fat and protein called lipoproteins. The two main lipoproteins that carry cholesterol throughout your blood:
- LDL (Low-Density Lipoprotein): Often called "bad" cholesterol. High levels can build up inside artery walls, raising the risk of heart attacks and strokes.
- HDL (High-Density Lipoprotein): Often called "good" cholesterol. It picks up excess “bad” cholesterol from tissues and takes it back to the liver to be cleared out.
To learn more about how standard cholesterol medications lower these numbers, read our guide on cholesterol, or browse our health articles.
Why Researchers Thought Raising “Good” Cholesterol Would Work
Inside your body the natural cholesterol transfer protein (CETP) acts like a trade system. It takes cholesterol away from helpful HDL packages and hands it over to the LDL packages. Years ago, large health studies showed that people born with higher HDL levels had fewer heart problems. Researchers came up with a theory that if a drug could block (inhibit) the CETP protein, cholesterol would stay trapped in HDL packages. They thought this would then boost HDL numbers and lower LDL numbers and create a positive impact on heart health. The idea was called the "HDL hypothesis" and it seemed to make complete and clear sense. Blocking CETP looked like a great way to tackle bad cholesterol and boost good cholesterol.
Torcetrapib: Why the First CETP Inhibitor Was Stopped
Big Changes in Cholesterol Numbers
The first major CETP drug to reach large patient studies was torcetrapib, which was made by Pfizer. Early tests showed big changes on blood tests. It raised HDL cholesterol by about 72% and lowered LDL cholesterol by about 25%.
Why Did Torcetrapib Fail?
To see if the lipoprotein number changes led to fewer heart attacks, researchers started the ILLUMINATE trial which looked at 15,067 high-risk patients. In December 2006, the trial was suddenly stopped due to safety concerns. Patients taking torcetrapib had more deaths and heart events than those taking their standard cholesterol medication (atorvastatin) alone. Later studies showed that torcetrapib had extra, unwanted and off-target side effects that had nothing to do with blocking CETP. The drug raised a hormone called aldosterone, altered blood minerals, and raised systolic blood pressure by an average of 5.4 mmHg. Researchers realized torcetrapib failed because of the drug's blood pressure side effects, not necessarily because blocking CETP was a bad idea.
Dalcetrapib: A Safer Molecule That Still Did Not Lower Heart Risks
A Safer Design with Minimal Impact
After torcetrapib failed, researchers designed a new CETP inhibitor that would not raise blood pressure. Roche developed dalcetrapib. Dalcetrapib was much safer because it did not cause blood pressure spikes or hormone problems. However, its effect on cholesterol was seen to be different. It was found to raise HDL by about 30% to 40%, but it barely changed LDL cholesterol at all.
What the dal-OUTCOMES Study Showed
Dalcetrapib was tested in the dal-OUTCOMES trial with 15,871 patients who recently had a heart attack or chest pain event. Patients were tracked for about two and a half years. In 2012, work on dalcetrapib was stopped because it was found that it did not lower one's risk of a heart attack. The conclusion here was that raising HDL cholesterol alone, without lowering bad cholesterol (LDL), was not enough to protect patients.
Note: Want to understand why changing cholesterol numbers doesn't always prevent heart events? Read our detailed blog on Why Some Cholesterol Drugs Prevent Heart Attacks and Others Do Not.
Evacetrapib: Strong Cholesterol Changes but No Clinical Benefit
The Biggest Surprise in CETP Research
Following this, Eli Lilly created evacetrapib, a strong CETP inhibitor built to change cholesterol without raising blood pressure. In tests, evacetrapib showed powerful numbers. It doubled HDL cholesterol and lowered LDL cholesterol by over 30%. It was seen to consistently alter both cholesterol numbers so many experts thought it would finally prove that CETP drugs work.
Why the ACCELERATE Study Was Stopped Early
The ACCELERATE trial tested evacetrapib in 12,092 high-risk patients for more than two years. In October 2015, experts stopped the trial early because evacetrapib was deemed unsuccessful. Even though patient lab tests showed dramatic cholesterol improvements, including a roughly one-third reduction in LDL ("bad") cholesterol and more than a doubling of HDL ("good") cholesterol, evacetrapib did not lower the rate of heart attacks, strokes, or cardiovascular deaths. The results surprised researchers and challenged long-held assumptions about cholesterol treatment. The study showed that even when a drug lowers bad cholesterol, raises good cholesterol, and appears safe, those lab changes do not automatically translate into fewer heart attacks or longer lives. One leading explanation involves apolipoprotein B (ApoB), a marker that reflects the number of cholesterol-carrying particles in the bloodstream. While evacetrapib removed a large amount of cholesterol from these particles, it reduced the actual number of harmful particles by only about 15%. Because these particles are what enter artery walls and drive plaque buildup, the modest reduction in particle number likely translated into only a small clinical benefit, too small to be detected during the study period. The key lesson from ACCELERATE is that improving cholesterol numbers alone is not enough. What appears to matter most is reducing the number of ApoB-containing particles in the blood, and maintaining that reduction over time.
Anacetrapib: The Drug That Worked but Was Shelved Anyway
Reaching Its Goal in the REVEAL Study
Next, Merck developed and tested anacetrapib in the REVEAL trial, which was a large study with 30,449 patients followed for over four years. Unlike the first three drugs, anacetrapib actually worked in its main trial and showed that taking anacetrapib alongside standard statins (atorvastatin) lowered major heart events by about 9% compared to a placebo (plus standard atorvastatin therapy).
Why Was Anacetrapib Never Approved?
Although it had a positive trial, Merck announced in late 2017 that it would not submit the drug for government approval. The 9% drop in heart risks was deemed as small given how long the trial ran. Additionally, tests showed that anacetrapib built up in body fat over time and stayed in tissue for years after a patient stopped taking it. The developer decided the overall profile was not strong enough to bring to the market and it was shelved before starting the approval process.
Are There Any Approved CETP Inhibitors?
Current Approval Status Around the World
As of November 2026, the status of CETP inhibitors depends on where you live.
- European Union: On September 21, 2026, the European Commission approved obicetrapib (sold as Ubeslo, or Evlarco when combined with ezetimibe). This is the world’s first approved CETP inhibitor.
- United States: Obicetrapib is not FDA-approved and is not available in the U.S.
Modern testing for obicetrapib is different from early CETP trials. Instead of trying to boost HDL, researchers are focused on how well it lowers bad markers like LDL, apolipoprotein B (ApoB), and Lipoprotein(a). Whether CETP inhibitors can lower heart risks long-term is still being looked at. Large studies, like the ongoing PREVAIL trial, are testing these outcomes now, with results expected in early 2027.
What 20 Years of Research Taught the Field
Lab Test Numbers vs. Actual Heart Health
Twenty years of CETP research taught experts a major lesson on how to assess new treatments. In heart health trials, researchers now track two different things:
- Surrogate Endpoints (Lab Numbers): Blood test numbers like HDL, LDL, or triglycerides.
- Hard Clinical Outcomes (MACE): This stands for Major Adverse Cardiovascular Events. MACE includes real-life events like heart attacks, strokes, emergency heart surgeries, and deaths from heart disease.
The biggest lesson from all four early CETP drugs is that we must grade heart medicines by their actual effect, which is whether they prevent real heart attacks and strokes, not just by how much they change numbers on a lab report. Note: Lowering cholesterol does not always mean lowering cardiovascular risk. Learn why some cholesterol drugs prevent heart attacks and others do not in our detailed blog, Why Some Cholesterol Drugs Prevent Heart Attacks and Others Do Not.
Overview of the Four Early CETP Drugs
Drug Name What Happened & What Researchers Learned Torcetrapib (Pfizer) Stopped (2006): Harmed patients due to off-target blood pressure side effects. Dalcetrapib (Roche) Stopped (2012): Raised HDL but failed to lower heart attacks; had almost no LDL effect. Evacetrapib (Lilly) Stopped (2015): Failed to lower heart attacks despite doubling HDL and lowering LDL. Anacetrapib (Merck) Shelved (2017): Met its goal (9% risk drop) but dropped because it built up in body fat. What Comes Next in Cholesterol Research
Today, research focuses less on total HDL and more on specific things that can carry risk:
- ApoB (apolipoprotein B): A protein tag found on all plaque-causing particles (a risk factor for cardiac events). Measuring ApoB may be a more accurate way to judge heart risk than standard LDL tests.
- Lp(a) (Lipoprotein(a)): A genetic form of LDL that drives plaque build-up (increasing the risk for cardiac events) and is not lowered much by regular statins.
Learning how new drugs affect these particles and being able to prove those changes prevent real heart attacks in trials like PREVAIL is where heart medicine is focused on today.
Questions? Talk to a Marley Drug Pharmacist
Managing cholesterol can feel confusing. While new treatments are studied in clinical trials, standard therapies like statins, ezetimibe, and other approved medications remain the proven way to protect your heart today. If you have questions about your cholesterol medicines or how your drugs work, the team at Marley Drug is here to help. You can speak with a pharmacist free of charge by calling 800-286-6781 or by visiting www.marleydrug.com. Disclaimer This article is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment. Always consult your healthcare provider or pharmacist regarding any specific health concerns or before starting, stopping, or changing any prescription drug. All information is current as of November 2026. References:
- Barter PJ, Caulfield M, Eriksson M, et al. Effects of Torcetrapib in Patients at High Risk for Cardiovascular Events. N Engl J Med. 2007;357(21):2109-2122.
- Schwartz GG, Olsson AG, Abt M, et al. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N Engl J Med 2012;367(22):2089-2099.
- Lincoff AM, Nicholls SJ, Riesmeyer JS, et al. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. N Engl J Med. 2017;376(20):1933-1942.
- HPS3/TIMI55-REVEAL Collaborative Group. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. 2017;377(13):1217-1227.
- Merck & Co., Inc. Merck Provides Update on Anacetrapib Development Program. News Release. October 11, 2017. Accessed November 3, 2026.
- European Medicines Agency (EMA). Ubeslo (obicetrapib) & Evlarco (obicetrapib/ezetimibe) European Public Assessment Report (EPAR). Published September 21, 2026. Accessed November 3, 2026.
- National Institutes of Health (NIH). A Study of Obicetrapib in Patients With Cardiovascular Disease (PREVAIL). ClinicalTrials.gov. Identifier: NCT05202509. Accessed November 3, 2026.