Semaglutide and Cardiovascular Outcomes in Overweight or Obese Individuals: The SELECT Trial

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The global rise in overweight and obesity poses a significant health challenge, with projections indicating that more than half of the world’s population will be affected by 2035. This epidemic has far-reaching consequences, with high body mass index (BMI) estimated to be responsible for 4 million deaths globally in 2015, the majority of which were attributed to cardiovascular diseases.

Despite the well-established link between overweight/obesity and cardiovascular risk, the approach to treating these conditions has been hindered by a lack of evidence supporting interventions that specifically target weight reduction to improve cardiovascular outcomes.

Background:

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. While standard evidence-based practices focus on managing risk factors such as dyslipidemia, hypertension, and diabetes, addressing obesity as an independent risk factor for cardiovascular complications has been a challenge. This is underscored by the fact that cardiovascular events continue to be a significant concern even after accounting for metabolic risk factors associated with excess weight.

GLP-1 Receptor Agonists in Diabetes Management:

Agonists of the glucagon-like peptide-1 (GLP-1) receptor have emerged as valuable tools in the management of type 2 diabetes and obesity. These agents, while primarily designed for glycemic control, have demonstrated an additional benefit in reducing the risk of major adverse cardiovascular events in patients with type 2 diabetes at high cardiovascular risk. However, the question remained whether GLP-1 receptor agonists could extend these cardiovascular benefits to individuals without diabetes but with overweight or obesity.

Semaglutide and Weight Reduction:

Semaglutide, a long-acting analogue of GLP-1, has shown promise in reducing body weight. Administered subcutaneously at a dose of 2.4 mg once weekly for 104 weeks, semaglutide led to a remarkable mean weight reduction of 15.2% in patients with overweight or obesity who did not have diabetes. This provided a compelling foundation for the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial.

The SELECT Trial:

The SELECT trial was designed to investigate whether the addition of semaglutide to standard care could surpass the efficacy of a placebo in reducing the risk of major adverse cardiovascular events. The study focused on individuals with overweight or obesity and preexisting cardiovascular disease who did not have diabetes.

Methodology:

The SELECT trial employed rigorous methodologies, including a randomized, double-blind, placebo-controlled design. Participants were administered semaglutide at a dose of 2.4 mg subcutaneously once weekly for a duration of 104 weeks. The study aimed to assess the impact of semaglutide on cardiovascular outcomes, taking into account the participants’ baseline characteristics, cardiovascular risk factors, and adherence to the treatment regimen.

Results and Implications:

The findings of the SELECT trial will provide critical insights into the potential role of semaglutide in reducing cardiovascular risk among individuals with overweight or obesity, independent of its effects on weight loss. If successful, this trial could reshape the approach to managing cardiovascular risk in this population, opening new avenues for the integration of GLP-1 receptor agonists into standard cardiovascular care.

Conclusion:

As the global burden of overweight and obesity continues to rise, addressing the associated cardiovascular risks becomes paramount. The SELECT trial holds the promise of elucidating whether semaglutide, a GLP-1 receptor agonist, can be a groundbreaking intervention in reducing major adverse cardiovascular events among individuals with overweight or obesity and preexisting cardiovascular disease. The results of this trial may usher in a new era in the comprehensive management of cardiovascular health in a population grappling with the consequences of excess weight.


More information: A. Michael Lincoff et al, Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2307563

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