A New Pill to Lower Cholesterol: The Promise of Obicetrapib + Ezetimibe 

Written By ClinicalConnections .

By Maria Poimenidou 

7/17/2025

For millions of people at risk of heart attacks and strokes, keeping "bad" cholesterol (LDL-C) in check is a daily challenge, even with the best available treatments. But a new study published in The Lancet offers a promising solution: a single pill that combines two cholesterol-lowering medications into one powerful daily dose. 

Why LDL Cholesterol Matters? 

LDL cholesterol is a major contributor to plaque buildup in arteries, which can lead to atherosclerotic cardiovascular disease (ASCVD), a leading cause of death worldwide. While statins are the gold standard for lowering LDL-C, they don’t work well enough for everyone. Some patients can’t tolerate high doses. Others avoid injectable treatments, which are more effective but less accessible. 

That’s where the TANDEM trial comes in. 

The TANDEM Trial: A One-Pill Powerhouse 

In this phase 3 clinical trial, researchers evaluated a fixed-dose combination (FDC) pill containing: 

  • Obicetrapib: a newer drug that blocks CETP, a protein involved in cholesterol transfer in the blood. 

  • Ezetimibe: a well-established medication that reduces cholesterol absorption in the gut. 

The study enrolled 407 adults in the U.S., all of whom had existing heart disease or were at high risk. Despite already being on the best cholesterol medications they could tolerate (excluding ezetimibe), their LDL-C levels remained too high. 

Participants were randomly assigned to one of four groups: the combo pill, obicetrapib alone, ezetimibe alone, or placebo. Over 12 weeks, they took their assigned pills without knowing which group they were in, a standard “double-blind” setup to ensure objectivity. 

The Results? Remarkable. 

The combo pill slashed LDL cholesterol by nearly 49% compared to placebo, significantly outperforming either drug on its own: 

  • Obicetrapib alone reduced LDL-C by ~32% 

  • Ezetimibe alone reduced it by ~20% 

  • Placebo had little effect 

More impressively, over 70% of patients taking the combo reached target LDL-C levels (<1.4 mmol/L). This is a key threshold for preventing cardiovascular events. Those numbers were far lower in the other groups. 

Beyond LDL-C, the combo pill also improved other markers of cardiovascular risk: 

  • Non-HDL cholesterol and apolipoprotein B (key components of “bad” cholesterol particles) dropped significantly 

  • HDL cholesterol (the “good” kind) rose substantially 

What About Safety? 

The pill was well tolerated. Side effects occurred in roughly half of participants across all groups, including those taking a placebo. Serious side effects were rare and evenly distributed. Importantly, the new therapy did not raise blood pressure, a concern with earlier CETP inhibitors that never made it to market. 

A New Option on the Horizon? 

The results suggest that this once-daily oral therapy could fill an important treatment gap. For patients who can’t reach their cholesterol goals with statins alone, or who avoid injections, this combo pill offers a potent, safe, and easy-to-use option. 

While longer-term studies are underway to assess cardiovascular outcomes, the early data are encouraging. If approved, obicetrapib combined with ezetimibe could be a game-changer in heart disease prevention. 

Disclaimer: This article summarizes findings from the TANDEM trial published in The Lancet (May 2025) and is intended for informational purposes only. Readers should consult healthcare professionals before making any treatment decisions. 

ClinicalConnections .