Efficacy and Safety of Enlicitide in Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Muhammad Farhan, Muhammad Murtaza, Muhammad Mujtaba Rasool et al.
✦ AI-curated · Sources linked
In 30 seconds
This systematic review and random-effects meta-analysis assessed efficacy and safety of oral enlicitide in adults with hypercholesterolemia. Three placebo-controlled randomized trials involving 3593 participants were included. Compared with placebo, enlicitide reduced LDL-C by a mean 56.19% (95% CI, -64.14 to -48.25; p < 0.0001). Reductions were also reported in non-HDL-C, apolipoprotein B, lipoprotein(a), and triglycerides, while adverse-event rates, serious adverse events, and treatment discontinuations were comparable between groups. The authors note that cardiovascular benefit remains unestablished and requires long-term outcomes trials.
Key findings
- Enlicitide reduced LDL-C versus placebo by a mean 56.19% (95% CI, -64.14 to -48.25; p < 0.0001).
- Mean reductions were reported for non-HDL-C (51.36%), apolipoprotein B (47.09%), lipoprotein(a) (20.10%), and triglycerides (13.12%).
- Adverse events, serious adverse events, and treatment discontinuations occurred at comparable rates between enlicitide and placebo groups.
- A numerical dose-response gradient was observed, but differences between dose subgroups were not statistically significant.
Why it matters
The findings suggest that an oral PCSK9 inhibitor can substantially lower LDL-C and other atherogenic lipid measures in adults with hypercholesterolemia, with safety outcomes comparable to placebo in the included trials. These lipid changes are surrogate outcomes, however, and do not establish that enlicitide reduces cardiovascular events; that benefit remains to be tested.
What to keep in mind
Only three trials were included, with moderate heterogeneity. The evidence relies on surrogate lipid endpoints, and exploratory dose-response and some lipid findings were substantially driven by single trials.