Oral Cholesterol Medication Shows Promise as Alternative to Injectable Treatments
A new daily oral medication called enlicitide demonstrated up to 60% reduction in LDL cholesterol in clinical trials, potentially offering a more convenient option for high-risk patients who struggle to reach cholesterol targets with current treatments.
For patients who have experienced heart attacks or strokes or are at high cardiovascular risk, a new daily oral medication may provide an effective alternative to injectable cholesterol-lowering therapies. The investigational drug enlicitide reduced LDL cholesterol by up to 60% in clinical trials, matching the effectiveness of existing injectable PCSK9 inhibitors while offering greater convenience for patients.
According to research presented at the American Heart Association's Scientific Sessions 2025, enlicitide represents a significant advancement for patients who cannot achieve recommended cholesterol levels despite lifestyle changes and standard medications like statins. Lead study author Ann Marie Navar, M.D., Ph.D., FAHA, emphasized that many patients struggle to reach guideline-recommended cholesterol targets with current therapies, leaving them at unnecessary risk of stroke and heart attack.
The phase 3 CORALreef Lipids trial enrolled 2,912 adults with an average age of 63 years, 39% of whom were women. All participants had experienced previous heart attacks or strokes or were assessed as being at intermediate or high risk for cardiovascular events. Despite being on stable lipid-lowering therapy, including statins for 97% of participants, their LDL levels remained above recommended targets.
After 24 weeks of daily treatment, participants taking enlicitide showed substantial improvements across multiple cholesterol markers. Beyond the 60% reduction in LDL cholesterol, the medication also produced a 53% reduction in non-HDL cholesterol, a 50% reduction in ApoB protein, and a 28% reduction in Lp(a) lipoprotein. The safety profile was comparable to placebo, with similar rates of serious side effects and few participants discontinuing treatment due to adverse effects.
Navar noted that enlicitide achieved almost identical cholesterol reductions to injectable antibodies alirocumab and evolocumab, with numerically better results than the siRNA medication inclisiran. This positions the oral medication as a potentially transformative option in cardiovascular care. The American Heart Association provides additional cardiovascular health information at https://www.heart.org.
The study's findings are particularly significant because current PCSK9 inhibitors, while effective, require injections that can be inconvenient for patients. These injectable medications work by blocking the PCSK9 protein from binding to LDL receptors, helping clear bad cholesterol from the bloodstream. Enlicitide represents the first oral medication that achieves similar effects through the same mechanism.
While these results are promising, researchers emphasize that the findings are preliminary until published in a peer-reviewed journal. An ongoing cardiovascular outcomes trial will determine whether the cholesterol reductions achieved with enlicitide translate to reduced risk of heart attacks and strokes. The CORALreef outcomes trial continues to evaluate the medication's potential to prevent major cardiovascular events, which will be crucial for determining its clinical utility.
For high-risk cardiovascular patients who have struggled to achieve cholesterol targets with existing treatments, enlicitide could eventually provide a more accessible and convenient option that maintains the effectiveness of current injectable therapies. The development of effective oral alternatives to injectable cholesterol medications represents an important step forward in cardiovascular disease management and patient care.