Population-level impact of semaglutide 2.4 mg in patients with obesity or overweight and cardiovascular disease: A modelling study based on the SELECT trial

Abstract

Aim: To estimate the impact of semaglutide 2.4 mg treatment on the risk of major adverse cardiovascular events (MACE) in adults with overweight/obesity in the United States based on the SELECT trial of patients with atherosclerotic cardiovascular disease.

Materials and methods: Using 2023 census projections and National Health and Nutrition Examination Survey data, we developed Markov population-based predictive models for US adults meeting SELECT inclusion criteria and, separately, for adults eligible for semaglutide 2.4 mg for its MACE risk reduction indication. The 10-year rate of recurrent MACE and deaths was estimated based on the Secondary Manifestations of ARTerial disease 2 risk calculator and estimated semaglutide 2.4 mg treatment effect as per the SELECT MACE hazard ratio.

Results: Of 6 164 019 US adults meeting the SELECT criteria, 2 523 218 (40.9%) are estimated to have ≥1 new MACE in the next 10 years with no additional intervention. Semaglutide 2.4 mg may prevent 496 400 events, a 16% relative reduction. An estimated 2 103 630 deaths are predicted over the next 10 years, of which 332 597 deaths (any cause, 16% relative reduction) could be avoided with semaglutide 2.4 mg. Among the estimated 22 653 158 meeting the MACE risk reduction FDA label criteria, 42.7% could experience ≥1 new MACE; treatment could prevent 1 934 493 MACE and 1 231 295 deaths (16% relative reduction for both).

Conclusion: Four in 10 individuals in the United States meeting the SELECT criteria are estimated to experience a recurrent CV event without additional intervention. Semaglutide 2.4 mg can potentially prevent between half a million and up to 2 million MACE over the next 10 years in the population meeting SELECT and MACE risk reduction eligibility.

Plain language summary: What is the context and purpose of this research study? More than 7 in 10 US adults have overweight or obesity, which increases the risk of heart disease. Semaglutide is a medication used to treat type 2 diabetes and obesity. A clinical study called SELECT found that semaglutide reduces the risk of heart attack, stroke, or death by 20% in adults with overweight or obesity and heart disease. What was done? Our research estimated how many people in the United States would meet the criteria for participation in SELECT, how many heart disease events they might have with regular medical care over the next 10 years, and how many could be avoided with semaglutide 2.4 mg treatment in addition to regular medical care. We also estimated how many people would still be alive if they were treated with semaglutide. We estimated the same information for all people eligible for treatment with semaglutide based on the US Food and Drug Administration (FDA) indication of semaglutide 2.4 mg in patients with heart disease. These estimations were based on a large survey of US adults. What were the main results? We found that over 6 million people would meet the SELECT study criteria. Of these, 41% are estimated to have at least 1 new heart disease event in the next 10 years. If treated with semaglutide 2.4 mg, nearly 500 000 heart disease events and more than 300 000 deaths could be avoided. More than 22 million adults would qualify for semaglutide 2.4 mg, according to the FDA indication. If all of these people were treated with semaglutide 2.4 mg, nearly 2 million heart disease events and more than 1 million deaths might be prevented. What is the originality and relevance of this study? Treatment with semaglutide 2.4 mg can reduce the risk of new heart disease events and death in patients with existing heart disease, showing a substantial impact of semaglutide treatment in a real-world setting in the United States. Our study used different analyses to add to the existing research about reducing the risk of heart disease in people with overweight or obesity.

Keywords: United States; cardiovascular disease; cardiovascular risk; glucagon‐like peptide‐1 receptor agonists; obesity; overweight; semaglutide.

FIGURE 1

Summary of the model development process (10‐year time horizon). BMI, body mass index; CV, cardiovascular; NHANES, National Health and Nutrition Examination Survey; SELECT, Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity; SMART, Secondary Manifestations of ARTerial disease; US, United States. *Civilian non‐institutionalized population.

FIGURE 2

Events avoided with semaglutide 2.4 mg* over the next 10 years in US adults in the overall cohort meeting SELECT trial inclusion criteria (of 6 164 019 individuals) aged 45 to <65 versus 65 years or older. CV, cardiovascular; MACE, major adverse cardiovascular events; SELECT, Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity; US, United States. *Events avoided based on HR of 0.8 for MACE end‐point, 0.81 for all‐cause mortality end‐point and 0.79 for heart failure hospitalisation.

FIGURE 3

Events avoided with semaglutide 2.4 mg* over the next 10 years in US adults in the overall cohort meeting SELECT trial inclusion criteria (of 6 164 019 individuals) with overweight versus obesity. BMI, body mass index; CV, cardiovascular; MACE, major adverse cardiovascular events; SELECT, Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity; US, United States. *Events avoided based on HR of 0.8 for MACE end‐point, 0.81 for all‐cause mortality end‐point and 0.79 for heart failure hospitalisation.