Lowering LDL can reduce cardiovascular risk. Whether obicetrapib can also protect memory is still an open question in Michael Davidson’s conversation with Peter Attia.
Davidson is a cardiologist and CEO of NewAmsterdam Pharma, which is developing the drug. That financial interest matters when weighing his expectations. Listen to the conversation.
LDL exposure adds up over a lifetime
Low-density lipoprotein, or LDL, carries cholesterol in the blood. LDL particles contribute to atherosclerosis, the buildup of plaque in artery walls. Both the amount of LDL and the years of exposure matter. Genetic studies and treatment trials support that causal relationship. European Atherosclerosis Society consensus.
Davidson argues for intervening earlier than a short-term risk score might suggest. Davidson’s prevention discussion.
A review of 26 trials tested statins, a class of cholesterol-lowering medicines. It found about a 22% reduction in the rate of major vascular events for each 1 mmol/L LDL reduction, about 39 mg/dL. These are two ways laboratories express blood cholesterol concentration. Follow-up was typically around five years. Cholesterol Treatment Trialists’ meta-analysis.
The absolute benefit depends on your starting risk. For scale, a hypothetical 22% relative reduction would move a 10% risk to 7.8% over the same period: about two fewer events per 100 people. That is illustrative arithmetic, not an individual forecast.
Our assessment: the evidence supports reducing cumulative LDL exposure. It does not establish one drug, dose, or LDL target for every APOE4 carrier. Nor does it make cardiovascular trial results proof of Alzheimer’s prevention.
Obicetrapib lowers LDL; outcomes are the next question
Obicetrapib blocks cholesteryl ester transfer protein, or CETP, which helps move cholesterol between particles in the blood. Blocking it can lower LDL cholesterol and raise high-density lipoprotein cholesterol, or HDL. CETP mechanism.
The size of the LDL effect depends on the trial and background treatment. In the early TULIP trial, obicetrapib, then called TA-8995, lowered LDL by about 45% at the two highest doses over 12 weeks.
The larger BROADWAY trial enrolled 2,530 people with established artery disease or inherited high cholesterol. They were already taking the cholesterol treatment they could tolerate. At day 84, LDL fell 29.9% with obicetrapib and rose 2.7% with placebo. The difference was 32.6 percentage points. That is why a blanket promise of 40–50% additional lowering overstates what this trial found.
Our assessment: a better cholesterol result is encouraging, but the history of CETP drugs makes clinical outcomes especially important. Two trials discussed in the episode show why:
| Trial | What happened | What it establishes |
|---|---|---|
| ACCELERATE: evacetrapib | At three months, LDL fell 31.1% and HDL rose 133.2% in the treatment group. Cardiovascular events occurred in 12.9% versus 12.8% with placebo over a median 26 months. | Large changes in cholesterol measurements did not deliver a demonstrated event benefit in this trial. |
| REVEAL: anacetrapib | Major coronary events occurred in 10.8% versus 11.8% with placebo over a median 4.1 years. | The reported 9% proportional reduction amounted to about one fewer event per 100 people. A CETP inhibitor can help, but each drug needs its own evidence. |
PREVAIL is the dedicated cardiovascular outcomes trial for obicetrapib. NewAmsterdam’s August 5, 2026 update reported more than 9,500 participants and an interim analysis planned for late 2026, with results expected in early 2027. Those dates are company forecasts. The same update reported a favorable European regulatory committee opinion, with a final European Commission decision still pending at that time. Dated development update.
The APOE4 finding is a blood-marker result
The Alzheimer’s question is whether changing cholesterol transport could also affect disease processes in the brain. The proposed mechanism remains unproven in people; a blood cholesterol change does not by itself demonstrate that brain cholesterol handling has improved. BROADWAY Alzheimer’s substudy.
The researchers measured p-tau217, a form of the tau protein in blood that tracks Alzheimer’s-related pathology. The published analysis included 1,535 participants with usable measurements and known ApoE status. Only 29 had two APOE4 copies. The analysis measured changes over 12 months, not memory performance or new dementia diagnoses. Published study and Table 1.
| Group | Change with obicetrapib | Change with placebo |
|---|---|---|
| All participants in the analysis | +2.09% | +4.94% |
| Carriers of at least one APOE4 copy, including people with one APOE2 copy | +1.92% | +6.91% |
| Two APOE4 copies, 29 people | −7.81% | +12.67% |
These are adjusted average changes in the blood marker, accounting for age and its starting level. In the first two rows, the marker rose more slowly; it did not fall. In the two-copy group, the difference between groups was 20.48 percentage points. That is not a 20% reduction in Alzheimer’s risk. Study Table 2.
The study also reports absolute blood-concentration changes, but neither measurement can tell us how many cases of dementia the drug might prevent. No clinical benefit was measured. The small two-copy subgroup, one-year follow-up, and many comparisons without adjustment for multiple testing all limit confidence in that striking subgroup result. Testing many outcomes increases the chance of a positive finding arising by chance. Study methods and limitations.
Our assessment: this is a reason for a prevention trial with memory testing and clinical outcomes. It is not a reason to treat APOE4 status alone with obicetrapib. Our BROADWAY explainer covers the biomarker question in more depth.
The diabetes discussion needs its full context
Davidson initially makes a broad claim about LDL-lowering drugs and diabetes. Attia challenges it by raising an exception, and Davidson distinguishes genetic findings from clinical results. The exchange is more qualified than a claim that every alternative to obicetrapib causes diabetes. The episode’s statin–diabetes discussion.
For statins, the effect is real and dose-dependent. In the 2024 trial meta-analysis, low- or moderate-intensity treatment produced new diabetes diagnoses in about 1.3% of participants per year versus 1.2% with placebo. That is roughly one additional diagnosis per 1,000 people per year. Most new diagnoses occurred in people already near the diagnostic threshold. Cardiovascular benefits remained evident in those same trials. Statin and diabetes meta-analysis.
That finding should not be generalized to every cholesterol medicine. The randomized FOURIER analysis of evolocumab did not establish increased new-onset diabetes. Nor did adding ezetimibe to a statin in the IMPROVE-IT analysis. Genetic evidence about lifelong differences is not interchangeable with the observed effects of taking a drug for a few years.
Attia and Davidson also favor using companion drugs instead of routinely maximizing statin doses. That is their clinical preference. It should not be read as proof that high-intensity statins are inappropriate: trials have demonstrated additional cardiovascular benefit from more intensive statin treatment. Their dosing discussion; statin trial evidence.
Fish oil results depend on the formulation
The episode also contrasts trials of different omega-3 preparations. The two fats discussed are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These were cardiovascular studies, not tests of Alzheimer’s prevention.
| Trial | Treatment and comparison | Cardiovascular events |
|---|---|---|
| STRENGTH | A prescription mixture of two omega-3 fats, EPA and DHA, versus corn oil | 12.0% versus 12.2%; no demonstrated benefit over roughly 3.5 years. |
| REDUCE-IT | Icosapent ethyl, a prescription EPA preparation, versus mineral oil | 17.2% versus 22.0% over a median 4.9 years, a 4.8-percentage-point difference. |
The trials differed in more than their products, so this is not a head-to-head comparison. REDUCE-IT also found more hospitalizations for atrial fibrillation or flutter, abnormal heart rhythms: 3.1% versus 2.1%. Its results do not establish equivalent benefits for an ordinary fish-oil supplement. REDUCE-IT results.
Bring a prevention question to your next appointment
A useful question is: given my cholesterol results, family history, blood pressure, glucose, and current treatment, what would most reduce my long-term cardiovascular risk? If a statin causes problems or is not getting you to an agreed target, ask about the trade-offs of adjusting it or adding another medicine. Our statin guide and lipid-panel guide can help you prepare.
Our distillation of the conversation: address the risks you can act on today, and let trials establish whether obicetrapib can protect memory. The episode offers a useful look at that research, not a personal treatment plan.