- LDL-C change at weeks 24 and 52;
- non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] at week 24;
- LDL-C goal attainment; and
- adverse events through week 52.1
In patients with eGFR below 60, placebo-adjusted LDL-C reductions were 65.9% at week 24 and 64.2% at week 52. In patients with eGFR of 60 or higher, the reductions were 62.3% and 56.8%, respectively. Enlicitide significantly reduced non–HDL-C, ApoB, and Lp(a) versus placebo in both groups (all P < .001). At week 24, 74.9% of enlicitide-treated patients with eGFR below 60 reached an LDL-C below 55 mg/dL, nearly identical to the 74.7% seen with eGFR of 60 or higher. The corresponding rates for an LDL-C below 70 mg/dL were 80.5% and 81.5%.1
“It has shown both efficacy and safety in patients with reduced eGFR,” Christie M. Ballantyne, MD, of Baylor College of Medicine, first author of the analysis, said in a comment to Pharmacy Times.
Safety was comparable to placebo, including in patients with eGFR below 60, according to the investigators. The abstract did not report adverse event rates by eGFR group. It also did not give separate results for patients with eGFR below 30 or those receiving dialysis.1
What the Label Says About Kidney Function
Enlicitide is minimally metabolized. After intravenous administration it is primarily eliminated via glomerular filtration, with about 73% of a dose recovered in urine. Even so, the prescribing information projects only 5%, 11%, and 26% higher steady-state exposure in patients with mild, moderate, and severe renal impairment, respectively. It also reports single-dose exposure is 17% and 75% higher in patients with end-stage renal disease when enlicitide is given before and after hemodialysis. The label describes none of these increases as clinically meaningful and includes no renal dosage adjustment.3
Patients with chronic kidney disease (CKD) commonly take several cardiometabolic medications. For them, the label reports that enlicitide did not affect exposure to lisinopril (Zestril, AstraZeneca; Prinivil, Merck), digoxin, warfarin, atorvastatin (Lipitor; Pfizer), levothyroxine, or oral semaglutide (Wegovy; Novo).3
Counseling Points for Patients With CKD
Administration is where pharmacists will spend most of their counseling time. Patients should swallow the tablet whole on an empty stomach in the morning with water, black coffee, or plain tea. They should then wait at least 30 minutes before other food or drink. Taking enlicitide 30 minutes after a meal cut steady-state exposure (AUC) by 48%.3
“In the phase 3 clinical trial program, there was good adherence to taking the medication first thing in the morning before food. It can be taken with other medications at the same time,” Ballantyne said. “The drug has a long half-life, so taking occasional doses non-fasting or missing an occasional dose is unlikely to make a major impact on efficacy.”
The label advises taking a missed dose as soon as possible, at least 30 minutes before the next food or drink other than water, black coffee, or plain tea, and not taking 2 doses on the same day.3
“Enlicitide provides a new nonstatin oral option [that] has been shown to be more effective than currently available nonstatin therapies with similar efficacy to the injectable monoclonal antibodies that target PCSK9,” Ballantyne said.
For now, pharmacists should present enlicitide as an LDL-C–lowering therapy. The CORALreef Outcomes (NCT06008756) trial has enrolled more than 14,500 participants and is evaluating whether the drug reduces cardiovascular morbidity and mortality; that benefit has not yet been established.2
