Key result
Oral PCSK9 inhibitors lower LDL-C by ~52% compared to placebo.
Why the study?
Do oral PCSK9 inhibitors reduce low-density lipoprotein cholesterol in adults with hypercholesterolemia on background lipid-lowering therapy?
Meta-Analysis (n=4,232)
Do oral PCSK9 inhibitors reduce low-density lipoprotein cholesterol in adults with hypercholesterolemia on background lipid-lowering therapy?
Mean Difference: -52.42 (95% CI -62.84–-42)
Oral PCSK9 inhibitors provide substantial short-term reductions in atherogenic lipoproteins without an apparent excess of short-term adverse events, supporting their potential as a simplified lipid-lowering therapy.
Oral PCSK9 inhibitors are emerging once-daily therapies intended to simplify PCSK9 pathway inhibition, but trial-level evidence varies across agents, populations, and follow-up. We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to February 5, 2026 for double-blind randomized trials comparing oral PCSK9 inhibitors with placebo on background lipid-lowering therapy. Five trials (n = 4232) evaluating AZD0780, NNC0385-0434, MK-0616, and enlicitide were included. Compared with placebo, oral PCSK9 inhibitors significantly reduced low-density lipoprotein cholesterol (mean difference, ‐52.42 percentage points; 95% confidence interval, ‐62.84 to ‐42.00) and ApoB (mean difference, ‐43.03 percentage points; 95% confidence interval, ‐52.12 to ‐33.94), with consistent reductions in nonhigh-density lipoprotein cholesterol and total cholesterol. High-density lipoprotein cholesterol was not significantly changed. No significant differences were observed in discontinuation due to adverse events, any adverse events, serious adverse events, or treatment-related adverse events. Oral PCSK9 inhibitors provide substantial short-term reductions in atherogenic lipoproteins without an apparent excess of short-term adverse events; longer-term cardiovascular outcome trials are needed.
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Abomohsen et al. (2026) conducted a meta-analysis in Hypercholesterolemia (n=4,232). Oral PCSK9 inhibitors vs. Placebo was evaluated on Low-density lipoprotein cholesterol (MD -52.42 percentage points, 95% CI -62.84 to -42.00). Oral PCSK9 inhibitors significantly reduced low-density lipoprotein cholesterol compared with placebo (MD -52.42 percentage points; 95% CI -62.84 to -42.00).
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