Can a Daily Pill Replace Cholesterol Injections?
Yes. In a phase 3 trial, a once-daily pill called enlicitide lowered LDL cholesterol by 57.1% at 24 weeks. That matches the results of injectable PCSK9 drugs that have been available for years, but in a simple pill you take by mouth.
For millions of people who struggle to control their cholesterol with statins alone, PCSK9 inhibitors have been a game-changer. The problem is that the current options, drugs like evolocumab (Repatha) and alirocumab (Praluent), require injections every two to four weeks. Many patients skip doses or avoid them entirely because of the needle. Enlicitide could change that by putting the same type of treatment into a daily pill.
What the Data Show
The CORALreef Lipids trial was a large, randomized, placebo-controlled phase 3 study. Here are the key findings:
- LDL cholesterol reduction: 57.1% drop at 24 weeks with enlicitide 20mg daily, compared to a 3% increase with placebo
- Non-HDL cholesterol: Significantly reduced compared to placebo
- Apolipoprotein B: Significantly reduced, an important marker tied to heart disease risk
- Lipoprotein(a): Also significantly lowered, a genetic risk factor that is hard to treat with other drugs
- Safety: The rate of side effects was similar between the drug and placebo groups
How It Works
Your liver uses a protein called PCSK9 to break down the receptors that pull LDL cholesterol out of your blood. When PCSK9 is blocked, more of those receptors stay active, and more LDL gets cleared. Injectable PCSK9 drugs use antibodies to block this protein. Enlicitide does the same thing, but it is a small molecule you swallow as a pill. It binds to PCSK9 in the bloodstream, just like the injections do.
Dr. Kumar’s Take
This is a big deal for cardiovascular medicine. PCSK9 inhibitors have already proven they reduce heart attacks and strokes, but the injection barrier is real. I have patients who qualify for these drugs but decline because they do not want another shot. An oral option that matches the same cholesterol-lowering power could open the door for a lot more people to get treated. That said, we still need long-term outcomes data. Lowering LDL is important, but what we really want to see is whether enlicitide reduces heart attacks and strokes the way the injectables have. Those trials are likely coming next.
Study Snapshot
- Trial name: CORALreef Lipids
- Design: Multinational, double-blind, randomized, placebo-controlled
- Drug: Enlicitide 20mg once daily (oral)
- Duration: 52 weeks (primary endpoint at 24 weeks)
- Developer: Merck
- Published: New England Journal of Medicine, February 5, 2026
Who Benefits Most
- People with high LDL cholesterol who cannot reach their goal on statins alone
- Patients at high risk for heart disease who need additional cholesterol lowering
- Anyone who qualifies for PCSK9 inhibitors but avoids the injectable versions
- People with elevated lipoprotein(a), which has few treatment options currently
Practical Takeaways
- Enlicitide is not yet approved or available by prescription. It is still in late-stage trials.
- If you are on a statin and your LDL is still above your target, talk to your doctor about your options.
- Do not stop or change any current medications based on this study.
- Ask your doctor whether your apolipoprotein B and lipoprotein(a) levels have been checked, as these are important and often overlooked markers.
Related Studies and Research
- Apolipoprotein B: A Better Predictor of Heart Disease Risk Than LDL Cholesterol? – directly relevant to understanding why ApoB matters in this study
- Single-Dose Psilocybin vs Placebo: First Double-Blind Depression Trial – another example of a well-designed placebo-controlled trial
- Mindfulness Meditation for Chronic Insomnia: Randomized Controlled Trial Results – another landmark randomized controlled trial
- Daily TMS Therapy: The Depression Treatment That Works in Just 6 Weeks – another treatment innovation changing patient access
FAQs
Is enlicitide available now?
No. It is still in clinical trials. If the remaining trials go well, it could be submitted for FDA approval in the coming years.
How does enlicitide compare to statins?
They work differently. Statins reduce cholesterol production in the liver. Enlicitide blocks PCSK9, which helps your body clear more LDL from the blood. They can be used together for an even bigger effect.
Are there side effects?
In this trial, side effects were similar between the drug group and the placebo group, which is encouraging. Long-term safety data is still being collected.
Will this replace injections like Repatha or Praluent?
It could for many patients. The cholesterol-lowering results are comparable. But the injectable drugs have years of long-term outcomes data showing they prevent heart attacks and strokes. Enlicitide still needs to prove that.
Bottom Line
A daily pill that cuts LDL cholesterol by 57% and matches the power of injectable PCSK9 drugs is a major step forward for heart health. Enlicitide could make effective cholesterol treatment much more accessible for patients who need it but avoid injections. We are waiting on long-term outcomes trials, but the early results from the CORALreef Lipids trial are very promising.
