Enlicitide decanoate represents the first oral formulation to successfully target PCSK9, achieving meaningful LDL cholesterol reductions in a 303-participant trial spanning 59 sites across 17 countries. The 20mg daily dose demonstrated efficacy in adults with heterozygous familial hypercholesterolemia who remained above target cholesterol levels despite statin therapy. This oral delivery mechanism potentially addresses the major barrier that has limited PCSK9 inhibitor adoption since the class's introduction with injectable monoclonal antibodies like evolocumab and alirocumab nearly a decade ago. The convenience factor could prove transformative for familial hypercholesterolemia management, where patients require lifelong aggressive cholesterol lowering but often struggle with injection-based regimens. However, the practical impact depends heavily on the magnitude of LDL reduction achieved—previous oral attempts at PCSK9 inhibition have failed to match the 50-60% reductions seen with injectables. The 52-week duration provides valuable safety data for this novel oral mechanism, though longer-term cardiovascular outcome studies will ultimately determine whether enlicitide can deliver the proven cardiovascular benefits established by its injectable predecessors. For the estimated 1 in 250 individuals with familial hypercholesterolemia, an effective oral option represents a significant therapeutic advancement.