A new experimental pill called enlicitide significantly lowers LDL cholesterol in high-risk patients already on statins, potentially offering an easier alternative to injected PCSK9 inhibitors.

In a randomized trial with over 2,900 participants, enlicitide reduced LDL cholesterol by up to 60% over six months, with benefits similar over a year and no notable safety differences versus placebo.

PCSK9 inhibitors are effective but underutilized due to administration method, cost, and prescribing complexity; enlicitide could address some of these gaps if approved.

The study is published in the New England Journal of Medicine in 2026 with DOI 10.1056/nejmoa2511002.

While results are promising, clinical outcomes like heart events and mortality require longer follow-up to be proven.

The NEJM report frames enlicitide as a potential new option for millions of high-risk patients.

Merck funded the study, and the FDA has placed enlicitide into an ultra-fast review program as it nears approval; large ongoing trials will determine if LDL lowering translates into fewer heart events.

Experts caution that LDL reduction alone has not yet shown a reduction in heart attacks, strokes, or death; ongoing trials with more than 14,000 participants aim to establish such outcomes.

The pill must be taken on an empty stomach, and longer-term data are pending, including Merck-led studies with over 14,000 participants.

Context: Heart disease is the leading cause of death, with high LDL cholesterol as a major risk factor; guidelines advocate lowering LDL to at least 70 mg/dL for high-risk individuals and even lower for very high risk.

Beyond LDL reduction, enlicitide also lowered non-HDL cholesterol, apolipoprotein B, and lipoprotein(a), suggesting broader lipid-related cardiovascular risk improvements.

There was no safety difference observed between enlicitide and placebo, though the dosing requires taking the pill on an empty stomach.