The Effects of Tirzepatide in People With Overweight/Obesity and Coronary Artery Disease

What Was Tested

The trial (phase 4) is built around Tirzepatide for atherosclerosis, cardiovascular disease & high blood pressure.

The objective of this study is to investigate, as a proof-of-principle, long-term (52 weeks) effects of tirzepatide once-weekly vs. placebo on changes in coronary plaque composition and progression (assessed by NIRS), plaque burden (assessed by IVUS) and microvascular function (assessed by invasively measured CFR) in overweight and obese individuals with stable coronary artery disease (CAD).

In addition, the objective of a baseline cross-sectional sub-study is to explore potential metabolic and cardiovascular (CV) predictors for high arteriosclerotic plaque burden in overweight and obese individuals and to establish a cohort for future research projects.

It had two arms (groups): Tirzepatide (experimental) and Placebo (placebo comparator).

Tirzepatide is administered sc. once-weekly.

Placebo is administered sc. once-weekly.

The registry classes the interventions as drug.

More on the Plan

As a proof of principle, it would be of scientific and clinical interest to explore the anti-atherogenic effect of tirzepatide in humans.

IVUS-NIRS imaging is uniquely suited for this purpose, as it makes it possible to detect changes in not only atheroma burden by IVUS but also to detect progression within the plaques in the lipidic/necrotic core component by NIRS.

LCBItotal allows for consecutive detection of small changes in the same individual, which is pivotal to explore the supposed antiatherogenic mechanism of tirzepatide with enough statistical power.

The investigators aim to investigate this hypothesis in a proof-of-principle study by investigating the change in coronary plaque composition in individuals with overweight or obesity and coronary artery disease (CAD) with high-risk characteristics by NIRS imaging randomised to 52-week treatment with tirzepatide or placebo.

Who Took Part

Enrollment: 124 planned participants were the target.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Informed written consent. BMI equal to or above 27 kg/m2. Age 18 years or older. Referred to coronary angiogram (CAG) due to stable angina. Coronary atheromatosis by angiography (obstructive or non-obstructive).

The full record lists 6 inclusion and 16 exclusion criteria; among the exclusions: treatment with glucagon-like peptide-1 receptor agonists (glp-1ra); history of coronary artery bypass surgery (cabg); planned cv intervention (including percutaneous coronary intervention, cardiac surgery or transcatheter valve intervention) at time of randomisation.

How the Study Was Run

Design: randomized, parallel-group and triple-blind.

Random assignment meant chance, not the researchers, decided who got Tirzepatide and who got the comparison, which limits bias.

The Tirzepatide group and the comparison group ran side by side rather than switching.

As a double-blind Tirzepatide study, the assignments were hidden from both participants and investigators until the end.

Those kept unaware of assignments: care provider, investigator and outcomes assessor.

It started in 2024-10-01 with completion listed for 2027-03-20.

It ran at 3 sites in Denmark (3).

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Lipid core burden index (time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:).

It also tracked 3 secondary outcomes, for example Percent atheroma volume (PAV), Number of high-risk coronary lesion and Coronary flow reserve.

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Tirzepatide in 124 people with atherosclerosis, cardiovascular disease & high blood pressure.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Tirzepatide compound page, Atherosclerosis, cardiovascular disease & high blood pressure research.