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The SELECT Trial looked at using semaglutide to lower the risk of major cardiovascular events (MACE) in people with overweight or obesity. The research reveals that semaglutide reduces the risk of heart attacks, strokes, and death from cardiovascular disease.
Obesity is a growing public health crisis affecting millions globally. Excess weight significantly increases the risk of developing multiple health problems, especially cardiovascular disease. Heart attack, stroke, and heart failure are more common in people with obesity. Therefore, strategies to reduce cardiovascular risk in this high-risk population are urgently needed.
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a promising option for weight management and improvement of cardiometabolic parameters. But what are the actual effects of semaglutide on cardiovascular event rates and outcomes?
The SELECT trial provides pivotal insights.
Semaglutide is an injectable drug that mimics the effects of GLP-1, a hormone released from the gut after meals. It binds to GLP-1 receptors in the pancreas, boosting insulin production while suppressing glucagon secretion. This lowers blood sugar levels.
Semaglutide also acts on GLP-1 receptors in the brain to increase feelings of fullness and reduce appetite. By decreasing calorie intake, semaglutide induces weight loss. The FDA has approved semaglutide for chronic weight management in adults with obesity or overweight.
Obesity is an independent risk factor for cardiovascular disease. It predisposes to atherosclerosis, hypertension, dyslipidemia, and diabetes - key drivers of heart attacks, strokes, and heart failure.
People with obesity have a greater risk of experiencing an adverse cardiovascular event. Heart disease is the leading cause of death in this population. Clearly, obesity is a state of heightened cardiovascular vulnerability requiring risk-reduction strategies.
The cardiovascular benefits of weight loss are well-established. But could semaglutide offer cardiovascular advantages beyond weight reduction alone?
This was the key question behind the SELECT trial.
SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) was an academic-led, placebo-controlled, double-blind trial across 4 continents. It aimed to definitively assess the cardiovascular effects of semaglutide 2.4 mg once-weekly in people with obesity.
With a cohort of over 17,000, it represents the largest trial to date evaluating a weight-loss medication’s cardiovascular impact. Experts hailed SELECT as a long-awaited study addressing a critical clinical and public health question.
Researchers randomly assigned over 17,000 participants to receive either semaglutide or a placebo injection once per week for around 2 years.
The participants included adults who were overweight or had obesity, and had existing heart disease or risk factors for heart disease, but did not have diabetes.
The main goal was to see if semaglutide could reduce the risk of major cardiovascular problems like heart attacks, strokes, and cardiovascular death (known as "MACE").
Researchers also looked at the effect on factors like hospitalization for heart failure, weight loss, and metabolic measures.
Key Findings: Semaglutide Greatly Lowered Cardiovascular Risk
The results, presented in 2021, were very positive. Compared to placebo, semaglutide lowered the risk of MACE by 20%. This protective effect was seen early and continued throughout the study.
Specifically, semaglutide also lowered the risk of:
Beyond that, semaglutide reduced hospitalizations for heart failure and unstable angina.
These impressive improvements occurred along with substantial weight loss. On average, participants lost about 15% of their starting weight.
This weight reduction likely played a role in the cardiovascular benefits. But semaglutide may provide heart protection in other ways too.
While diminished weight and favorable metabolic changes mediate some of semaglutide’s cardiovascular protection, additional mechanisms are likely involved.
In lipolysis experiments, semaglutide exhibited anti-inflammatory effects in human adipose tissue – beneficial for atherosclerosis. Animal studies reveal direct cardioprotective actions such as lessening ischemia-reperfusion injury.
Furthermore, the cardiovascular risk reduction with semaglutide exceeded that anticipated from the degree of weight loss alone. This strongly suggests protective effects beyond just weight change.
Teasing out the weight-independent cardiovascular effects of semaglutide merits further research. But the totality of evidence demonstrates robust cardiovascular advantages.
Based on SELECT, semaglutide provides broad cardiovascular protection in people with overweight/obesity, both with and without established cardiovascular disease.
Some subgroups with very high baseline cardiovascular risk appeared to gain even greater risk reduction with semaglutide. For example, patients with preexisting peripheral artery disease saw a 40% lower risk of MACE.
People with obesity plus the following characteristics may be strong candidates for semaglutide to mitigate cardiovascular risk:
| Established Atherosclerotic Cardiovascular Disease | Individuals with a history of cardiovascular disease are considered strong candidates. |
| Hypertension or Hyperlipidemia | These conditions are associated with increased cardiovascular risk and align with the profile of candidates for semaglutide. |
| Family History of Premature Cardiovascular Disease | A family history of premature cardiovascular disease indicates higher risk. |
| Diabetes or Prediabetes | While the SELECT trial focused on individuals without diabetes, those with prediabetes are relevant candidates due to elevated cardiovascular risk. |
| Severe or Longstanding Obesity (BMI ≥40 kg/m²) | Severe or longstanding obesity is a recognized criterion for considering semaglutide treatment. |
| Abdominal Adiposity | Central obesity is a significant risk factor for cardiovascular disease and aligns with the treatment goals of semaglutide. |
The benefits observed even in patients with relatively modest degrees of overweight is supported by the SELECT trial findings, which indicate that semaglutide can provide cardiovascular benefits across a range of BMI categories.
In the SELECT trial, discontinuation rates due to adverse events were higher with semaglutide compared to placebo. This is an important consideration when prescribing semaglutide.
Gastrointestinal side effects like nausea, vomiting, and diarrhea occurred more frequently with semaglutide. However, these symptoms generally improved over time in most patients.
Cases of severe hypoglycemia were rare in SELECT, but remain a potential risk to monitor, especially in diabetic populations.
Diabetic retinopathy complications were uncommon in both groups. However, retinopathy is a consideration with semaglutide use in diabetic patients.
The SELECT trial demonstrated significant cardiovascular benefits with semaglutide in people with obesity. However, a careful assessment of safety and individual factors is important when determining if semaglutide is an appropriate treatment option. Healthcare providers should consider both the benefits and potential risks on an individual patient basis.
In 2021, the FDA officially approved semaglutide 2.4 mg for chronic weight management in individuals with overweight or obesity. An FDA advisory committee had previously voted overwhelmingly to recommend this approval, concluding that the evidence was persuasive for significant weight loss efficacy along with cardiovascular risk reduction.
On the heels of SELECT, numerous ongoing trials are further evaluating semaglutide. Areas under investigation include:
SELECT provides a robust foundation supporting first-line use of semaglutide for cardiovascular risk mitigation in clinical obesity care. However, additional research will refine these applications.
Updated treatment guidelines are likely to position GLP-1 receptor agonists like semaglutide as preferred anti-obesity agents for patients with heightened cardiovascular risk. This paradigm shift promises to improve the historically dismal cardiovascular prognosis in obesity.
Obesity is a cardiovascular disease in its own right. Landmark SELECT trial results indicate semaglutide is highly effective at reducing the heightened cardiovascular event rate associated with excess weight.
Beyond significant weight reduction, semaglutide demonstrates multifactorial cardiovascular protection – decreasing the risk of heart attack, stroke, heart failure, hospitalization, and cardiovascular death. Benefits extend to those with and without established heart disease.
While long-term outcomes data remains limited, the favorable safety profile observed makes semaglutide an attractive option to mitigate cardiovascular risk in appropriately selected patients with overweight or obesity. This novel therapeutic approach could substantially lessen the burden of cardiovascular disease in a high-risk population.
Schedule your semaglutide consultation today at Dr. V Medical Aesthetics to discuss reducing cardiovascular risk through clinically meaningful weight loss
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