Ann Pharmacother. 2026 Oct 14:10600280261494015. doi: 10.1177/10600280261494015. Online ahead of print.
ABSTRACT
OBJECTIVE: This article describes pharmacology, pharmacokinetics, safety, and efficacy data of enlicitide, the first Food and Drug Administration (FDA)-approved oral proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i).
DATA SOURCES: PubMed, Embase, Web of Science, and Cochrane were searched through July 17, 2026.
STUDY SELECTION AND DATA EXTRACTION: Clinical trials published in English were included. Relevant information from the methodology and results was extracted.
DATA SYNTHESIS: Enlicitide received FDA approval on July 16, 2026, based on results from phase 2 and 3 trials showing a 57.1% to 64.6% reduction in low-density lipoprotein-cholesterol (LDL-C) and reduced other atherogenic lipid particles at 24 weeks in patients with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia, while maintaining a favorable adverse effect profile. Enlicitide represents the fifth FDA-approved agent targeting PCSK9, having similar efficacy to other agents in class while having a novel macrocyclic peptide formulation with permeation enhancers, allowing for oral administration.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:As PCSK9is continue to be at the forefront of dyslipidemia guidelines, the approval of an oral agent is paramount in ensuring patient access. Enlicitide mirrors LDL-C lowering compared with existing PCSK9is and surpasses LDL-C lowering compared with non-statin options such as bempedoic acid and ezetimibe. Confirmation of cardiovascular outcomes data with enlicitide will solidify its role in reducing atherosclerotic cardiovascular disease risk.
CONCLUSION: Enlicitide significantly lowered LDL-C similar to existing PCSK9is with few adverse effects. The oral formulation provides an essential option for LDL-C lowering, especially in patients adverse to injections.
PMID:42870623 | DOI:10.1177/10600280261494015