Semaglutide 2.4 mg Could Reduce US Obesity by Half, Prevent 1.5 million CVD Events

More than 90 million US adults with overweight or obesity are candidates for weight loss treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide 2.4 mg (Wegovy, Novo Nordisk), according to calculations from investigators at the University of California, Irvine (UC Irvine).¹

The research team, led by Nathan D. Wong, PhD, director of the Heart Disease Prevention Program at UC Irvine, also suggests that not only could weight management treatment of this nature reduce by nearly 50% the size of the current US population with obesity, it could also prevent as many as 1.5 million cardiovascular disease events over 10 years of use.¹

Findings from the study, published online August 14 in Cardiovascular Drugs and Therapy, come approximately 2 weeks after Novo Nordisk announced topline results from the SELECT cardiovascular outcomes trial with semaglutide 2.4 mg that suggest the incretin mimetic may reduce the risk of major adverse cardiovascular events in adults with overweight or obesity and established cardiovascular disease (CVD).

Semaglutide was approved by the US Food and Drug Administration for chronic weight management in June 2021 and originally for management of hyperglycemia in persons with type 2 diabetes in December 2017.  

“We now have a weight control therapy that also significantly reduces cardiovascular events beyond the diabetes population where it was originally studied,” said Wong in a UC Irvine release.² “It should be considered for patients who are obese or overweight with other risk factors where cardiovascular disease is their leading cause of disability and death.”²

According to the authors, the objective of the current study was to project the population-wide impact of semaglutide 2.4 mg on weight loss and prevalence of obesity and further to estimate the potential reduction in 10-year CVD risk.¹

First, to identify the US population eligible for treatment with the drug, Wong and colleagues applied inclusion criteria from the semaglutide STEP 1 obesity management trial (see figure) to data on US adults aged ≥18 years from the US National Health and Nutrition Examination Survey (NHANES) cycles from 2015 to 2018.

FINDINGS

Of the 19 225 individuals in the NHANES from 2015-2018, the research team identified 3999 who matched STEP 1 trial eligibility criteria and comprised the sample for analysis. The sample was projected to represent 93.0 million US adults.¹

Weight loss, disease prevalence

Based on treatment effects observed in the STEP 1 trial, investigators then estimated the proportion of adults in their projected sample of 93 million that would be expected to achieve similar results. Wong and colleagues found that 86.4% could achieve ≥5% loss of body weight, 69.1% could achieve a reduction of ≥10%, and 50.5% could expect to achieve weight reduction of ≥15%. They calculated further that even if their estimates accounted for a placebo effect, 41.9 million persons would be expected to reach a weight reduction of ≥15% and 51.8 million reduction of ≥10%.

The researchers also observed that the overall prevalence of obesity in the US could be reduced by nearly half (46.1%), translating to 43 million fewer adults with obesity and many of those shifting to the category of overweight. The percentage of their sample expected to be within a normal weight range was 16.8%, or 17.5 million adults.¹

10-year CVD risk

Wong and colleagues’ estimate of 10-year CVD risk reduction in the projected sample was based on the 3493 adults without prior CVD (projected 83 million). Using BMI-based Framingham CVD risk scores, 10-year risk before they applied semaglutide 2.4 mg treatment effects was 10.15% and reduced to 8.35% after they were applied. These values reflect an absolute risk reduction of 1.81% and relative risk reduction of 17.8%, percentages that translate to 1.50 million preventable CVD events over 10 years.

Referring to semaglutide as “one of the biggest advances in the obesity and cardiovascular medicine world,” Wong also points out the significant potential for the GLP-1 receptor agonist and drugs like it to reduce the exorbitant cost burden to the health care system of both classes of disease.

The investigators acknowledge several study limitations including potential differences among NHANES and STEP 1 populations that could manifest as lower overall CVD risk in the sample and also as different treatment responses. Also, while the Framingham Risk scores are a standard for CVD event estimation, they lack the accuracy of documenting actual CVD events as would be captured in a cardiovascular outcomes trial.

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References:

1. Wong ND, Karthikeyan H, Fan W. US population eligibility and estimated impact of semaglutide treatment on obesity prevalence and cardiovascular disease events. Published online August 14, 2023. Cardiovasc Drugs Ther. 2023. doi:10.1007/s10557-023-07488-3

2. Popular weight loss medication may benefit 93 million U.S. adults, UC Irvine study found. UCI News. News release. August 14, 2023. Accessed August 21, 2023. https://news.uci.edu/2023/08/16/popular-weight-loss-medication-may-benefit-93-million-u-s-adults-uc-irvine-study-found/.

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