A new reading of the SELECT clinical trial consolidates that Ozempic-type drugs, based on semaglutide, provide cardiovascular protection in overweight or obese people who already suffer from heart disease. The results, published in The Lancet, reinforce that the effect is beyond weight loss, a key nuance for clinical practice.
In this analysis, the drug significantly reduced major adverse cardiovascular events, with a drop in 20% in heart attack, stroke or cardiovascular deathThe improvement did not depend on how many kilos each participant lost and, in fact, the reduction in waist circumference only explained around one third of the total profit.
What the new SELECT analysis brings
SELECT included more than 17.600 people over 45 years old, with body mass index (BMI) ≥27 and established cardiovascular disease, recruited in 41 countries. Participants, all without diabetes, received weekly injections of semaglutide or placebo and were followed for more than two years.
Compared with placebo, semaglutide reduced major adverse cardiovascular events (MACE) by 20%This effect was consistent regardless of initial weight and the amount of weight lost at follow-up, underscoring that the protection It is not explained only by losing weight.
The analysis separated the role of weight and waist circumference. While changes in weight had limited predictive value, each reduction of about 5 centimeters in waist was associated with a drop of approximately 4% in cardiovascular risk, explaining about 33% of the treatment benefit; the remainder points to other mechanisms.
According to the team led by John Deanfield (UCL), abdominal fat is particularly harmful to the heart and reducing it is important, but there are still two-thirds of the protective effect without a single pathway to explain it. This opens the door to direct cardiovascular mechanisms of semaglutide in tissues and vessels.
Possible mechanisms beyond the scale
Semaglutide is a GLP-1 receptor agonist, a hormonal pathway that regulates appetite and blood glucose after meals. Beyond weight control, evidence suggests favorable effects on vascular inflammation, endothelial function and hemodynamic and lipid parameters.
- less inflammation: decrease in proinflammatory cytokines that damage arteries.
- Better blood pressure and lipids: favorable impact on tension and HDL cholesterol and LDL.
- Endothelial function more competent: vessels with better dilation capacity.
For Deanfield, these results "reconfigure" the vision of the drug: it would not only be a treatment for weight loss, but also a cardiovascular protection tool direct in patients with established disease.
Clinical implications in Spain and Europe
Specialists in our environment, such as Antonia Delgado (Gregorio Marañón Hospital), indicate that abdominal perimeter reflects visceral fat, which is closely linked to heart attacks and strokes. José Luis Zamorano (Ramón y Cajal Hospital), the data support a cardioprotective effect of its own; and Cristóbal Morales (Vithas Sevilla Hospital) highlights its value in cardiovascular prevention in patients with BMI ≥27 and cardiac pathology.
If confirmed and transferred to guidelines, semaglutide could expand its indication to overweight profiles with a high cardiovascular risk, even if they do not achieve significant weight loss. In Europe, some health systems have begun to evaluate its use with this approach, while in Spain its possible financing in secondary prevention scenarios is being debated.
The potential health impact is significant: cardiovascular diseases remain the first cause of death in our country. A drug capable of reducing serious events in patients with established disease, regardless of the weight lost, represents an opportunity for reduce care load and improve quality of life, and can be complemented with technologies such as a watch that detects heart attacks.
Limitations and cautions
SELECT did not include people with diabetes and was funded by Novo Nordisk, the drug's manufacturer. Furthermore, the cohort had limited diversity—white men predominated—so it requires analysis by sex and ethnicity and more data in other groups.
For now, solid evidence is limited to adults with BMI ≥27 and established cardiovascular disease. Uses in people without excess weight or in primary prevention need specific tests before considering large-scale indication changes.
The overall picture left by the SELECT data is clear: Ozempic-type drugs provide substantial cardiovascular benefit in patients without diabetes and who are overweight or obese, and this effect does not depend on the number on the scale; the waistline matters, but it does not explain everything, which points to cardiometabolic mechanisms that research is already beginning to unravel.