UC Irvine researchers project cardiac benefits from weight-loss medication tirzepatide

New study finds that popular weight-loss medication may reduce the number of U.S. adults with obesity by 55 million and prevent up to 2 million heart attacks and strokes over a 10-year period.

Irvine, CA – June 10, 2024 – Researchers from the University of California, Irvine have just published a study that projects 93 million U.S. adults who are overweight and obese may be suitable for tirzepatide, marketed as a weight-loss medication under the brand name Zepbound. They projected that based on the known weight-loss and cardiovascular risk factor effects of this therapy that its use could result in 55 million fewer people with obesity and prevent up to 2 million heart attacks, strokes and other adverse cardiovascular events over 10 years.

The study, “U.S. Population Eligibility and Estimated Impact of Tirzepatide Treatment on Obesity Prevalence and Cardiovascular Disease Events,” published today in the journal Cardiovascular Drugs and Therapy was led by Nathan D. Wong, PhD, professor and director of the Heart Disease Prevention Program in the Division of Cardiology at the UC Irvine School of Medicine. It was also presented at the American Heart Association scientific sessions in November 2023.

The analysis is based on tirzepatide eligibility criteria and results from the SURMOUNT-1 trial, published in 2022 in The New England Journal of Medicine, which showed that tirzepatide, approved last year by the FDA for the treatment of obesity, reduced bodyweight up to an average of 21% on the highest 15-milligram dosages along with reductions in several cardiovascular risk factors such as blood pressure and cholesterol. 

The study projected that 93 million U.S. adults (based on National Health and Nutrition Examination Survey data) who are overweight or obese would fit SURMOUNT-1 eligibility criteria and that treatment with the drug would result in 55 million fewer persons with obesity based on the 15-milligram dosage. Wong and colleagues applied body mass index and other risk factor changes to cardiovascular disease risk scores among an estimated 93 million persons without pre-existing cardiovascular disease, estimating a reduction in 10-year cardiovascular disease risk from 10.1% to 7.7% (with a relative risk reduction of 23.6%), projecting up to 2 million cardiovascular events could be potentially prevented over a 10-year period. 

“Our projected 24% reduction in cardiovascular events in persons with overweight or obesity but without cardiovascular disease from tirzepatide compares favorably to the well-publicized SELECT trial published last year involving another weight-loss medication Wegovy (semaglutide 2.4 milligram ), which was studied in persons with cardiovascular disease and showed a 20% reduction in future cardiovascular events,” said Wong, who also previously published a similar analysis of semaglutide estimating an 18% risk reduction in persons without cardiovascular disease. “These newer obesity therapies as well as well as others in development that also have promising cardiovascular risk reduction benefits are among the most important developments in obesity and cardiovascular medicine in the past decade.” 

The SURMOUNT-MMO trial testing the effects of tirzepatide on actual cardiovascular outcomes in persons with overweight and obesity both with and without prior cardiovascular disease is currently in progress and expected to read out in 2027. According to Wong, “This trial will be crucial to determine the effects of tirzepatide on actual cardiovascular outcomes in this population and will be important to validate the estimated effects in our study.”

Wong also noted that his analysis of tirzepatide was estimated based on effects seen at the highest 15-milligram dosage and that not all patients may be titrated to nor tolerate of the maximum dosage, so estimated benefits may be less at lower dosages.

Since drugs in this class have side effects, it is important that patients always discuss the risks and benefits of such therapies with their physician. Additionally, an appropriate dietary and physical activity regimen is always the foundation of weight management and cardiovascular risk reduction. Moreover, access and supply issues for these therapies remain a challenge, especially among our high-risk underserved populations who may benefit most from them.

Zepbound is a combined glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist approved by the FDA for chronic weight management in adults who are obese or overweight with at least one weight-related condition, such as high blood pressure, type 2 diabetes, high cholesterol, or cardiovascular disease and is to be used in addition to a reduced calorie diet and increased physical activity. Moreover, tirzepatide is marketed under the same dosages for persons with diabetes under the brand name Mounjaro.

Co-authors with Wong on this paper included Hridhay Karthikeyan, MS and Wenjun Fan, MD, MS, PhD, also with the UC Irvine.

Grant Information: Funding for the study was supported by Lilly.

Conflict of Interest Disclosures: Wong receives research funding through his institution from Novo Nordisk, Lilly, and Novartis. He is also a consultant for Novartis and Amgen.

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