[00:00.4]
Hello, colleagues, I'm Professor Subodh Verma from the University of Toronto, here in Madrid at the ESC meeting where we presented as a late breaker, the results of SEMA-VR, a translational clinical trial evaluating the effects of semaglutide on vascular regenerative flux in humans.

[00:18.1]
These data were also published simultaneously in the European Heart Journal.

[00:26.1]
Now, let me tell you about this SEMA-VR translational, randomised study. As you all know, semaglutide is a GLP1 receptor agonist. It has been suggested to have cardiovascular benefits in people living with obesity, as well as people with diabetes.

[00:42.3]
So many clinical trials have been done, including SUSTAIN 6, the PIONEER 6 programme, SELECT, STRIDE was a trial that I was involved in very intimately. All of these trials have led to a very clear understanding that GLP1 receptor agonists, such as semaglutide, are antiathrosclerotic medications, they're vascular protective medications.

[01:07.7]
That remains really irrefutable. The question, however, is how does this magic work? What are the biological underpinnings? Is it weight, is it inflammation? You know, are there other direct potential vascular benefits that are mediating this effect?

[01:24.5]
We've actually had very little data in humans to inform us around this question. So we did a randomised, translational study called SEMA-VR, in which we took people living with obesity or diabetes with risk factors. We randomised them to receive semaglutide versus usual care.

[01:43.1]
And our primary endpoint here was looking at vascular regenerative stem cell flux. And you may wonder, oh my God, what is that? Well, it turns out that blood vessel repair and regeneration is a very important determinant of atherothrombosis.

[01:59.8]
And the blood vessels repair themselves through multiple mechanisms, but there is a population of stem cells within the bone marrow that actually play a very important role in this reparative process. And we know that cardiometabolic diseases are associated with a reduction in this reparative flux.

[02:19.8]
And because of that reduced reparative flux, that can really set up the blood vessel for increased risk of atherothrombotic events. So our group has the ability to really in real time evaluate the flux of these vascular progenitor stem cells.

[02:38.4]
And we do that using ALDH high flow cytometry analyses and also lineage tracking for the cell specific markers. And what we found was, over 6 months, semaglutide was associated with a increased number of these vascular reparative progenitor cells.

[02:59.3]
And we also found that granulocyte precursors were reduced and these are the so-called inflammatory cells. In addition to that, cytokines like interleukin and TNF-alpha were also attenuated with semaglutide. So what does this all mean?

[03:14.6]
It means that even within 6 months of treatment with a GLP1 receptor agonist in people with cardiometabolic diseases, there wasn't that much weight reduction. There wasn't that much change in haemoglobin A1c. But the flux of bone marrow repair that drives repair of blood vessels was favourably improved.

[03:38.3]
There was an anti-inflammatory response that was observed, and all of this suggests or supports sort of the thesis that there are direct benefits of GLP1 receptor agonists not just on blood vessels, but also on how the body responds to stress and how the body repairs blood vessels, which is an inherent and important determinant of overall vascular homeostasis and vascular health.

[04:05.5]
So I think this adds further support to the notion that these truly are vascular protective strategies in addition to all of their other benefits on weight haemoglobin A1c, you know, and all of the plethora of benefits that are emerging.