Enlicitide shows sustained lipid lowering in patients with or at risk of ASCVD

Enlicitide versus placebo demonstrated significant and sustained reductions in low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipids, together with high treatment adherence, according to a pooled analysis of phase 3 trials reported by Prof. Ann Marie Navar (University of Texas Southwestern Medical Center, TX, USA) [1].

CORALreef Lipids (NCT05952856) and CORALreef HeFH (NCT05952869) were similarly designed phase 3, randomised, controlled trials assigning patients in a 2:1 ratio to enlicitide or placebo for 52 weeks. Participants were eligible if they had a history of major atherosclerotic cardiovascular events with LDL-C levels ≥55 mg/dL or were at risk for such events with LDL-C levels ≥70 mg/dL. In both trials, background therapy consisted of an optimised, stable statin with or without other lipid-lowering therapies. Outcomes included changes in lipid parameters at weeks 24 and 52. The total pooled population was 3,207 patients.

At week 24, enlicitide led to a mean reduction of 60.4% in LDL-C, compared with a 3.0% increase in LDL-C in the comparator (least-squares mean between-group difference -63.6%; 95% CI -66.0% to -61.2%). These results were further maintained through week 52 in the pooled population. Significant reductions with enlicitide were also observed in non-HDL-C, apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) at both at weeks 24 and 52. Treatment adherence, defined as following all dosing instructions with no more than 1 missed day per week, was self-reported at a rate of 98%.

“Enlicitide provided significant and sustained LDL-C lowering through week 52,” concluded Prof. Navar. “Patients who remained on treatment achieved a 64% placebo-corrected reduction at week 24 and 60% at week 52. The high degree of self-reported adherence to dosing instructions is corroborated by the sustained LDL-C lowering observed in this analysis.”

Navar AM et al. Durability of enlicitide for lipid lowering: On-treatment analysis of data from CORALreef Lipids and CORALreef HeFH trials. ACC 2026, 28–30 March, New Orleans, LA, USA.