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The SELECT Trial: Semaglutide’s Impact on Cardiovascular Health in Non-Diabetic Patients 

Model of Heart

The SELECT trial has provided significant insights into the cardiovascular benefits of semaglutide, a GLP-1 receptor agonist, for individuals who are obese or overweight and do not have diabetes. This study aimed to determine whether semaglutide could reduce the incidence of major adverse cardiovascular events (MACE) in this population. Here’s a concise overview of the key findings and possible mechanisms behind the results. 

Model of Heart

Key Findings from the SELECT Trial 

The SELECT trial involved 17,604 participants, all adults aged 45 and older with a body mass index (BMI) of 27 kg/m² or higher and established cardiovascular disease, but no history of diabetes. The primary objective was to see if semaglutide could lower the risk of MACE, which includes heart attacks, strokes, and cardiovascular deaths. The findings were as follows: 

  • Risk Reduction: Semaglutide reduced the risk of MACE by 20% compared to placebo. 

– Primary Outcome: The incidence of MACE was 6.5% in the semaglutide group versus 8.0% in the placebo group. 

– Heart Attack: Risk was reduced by 21%. 

– Stroke: Risk was reduced by 20%. 

– Cardiovascular Death: Risk was reduced by 19%. 

These results suggest that semaglutide can significantly improve cardiovascular outcomes in non-diabetic individuals with obesity or overweight conditions and a history of cardiovascular disease. 

Possible Explanations for Reduction in MACE 

Several mechanisms may explain the reduction in cardiovascular events observed with semaglutide: 

1. Weight Loss: Semaglutide promotes significant weight loss, which can reduce cardiovascular strain and lower risk. 

2. Improved Glycemic Control: Improved insulin sensitivity and reduced blood sugar levels, even in non-diabetic patients, can lower cardiovascular risk. 

3. Anti-inflammatory Effects: Semaglutide may reduce vascular inflammation and slow the progression of atherosclerosis. 

4. Improved Lipid Profile: The drug may lower LDL cholesterol and triglycerides, key factors in cardiovascular disease. 

5. Blood Pressure Reduction: Weight loss and direct effects of semaglutide can lead to lower blood pressure. 

6. Direct Cardiovascular Effects: GLP-1 receptor agonists may improve endothelial function and reduce the risk of plaque rupture. 


The SELECT trial’s findings indicate that semaglutide can significantly reduce the risk of major adverse cardiovascular events in non-diabetic individuals with obesity or overweight conditions and established cardiovascular disease. By understanding the mechanisms behind these benefits, healthcare providers can better assess the potential role of semaglutide in managing cardiovascular risk in this population. 

Semaglutide (Wegovy) vs. Tirzepatide (Mounjaro): Which is the Better Weight Loss Medication? 

There are no direct head-to-head trials between semaglutide (Wegovy) and tirzepatide (Mounjaro). So, what we have to date is like comparing two world-class boxers and asking who is the best, when they have never actually fought each other. This study uses statistical analysis to virtually “match” and “pair-up” participants in different trials to provide a better comparison of the effectiveness of the two drugs.

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