What has now happened, particularly with the STRIDE study, it has reminded us of the importance of PAD in the diabetes space. So overall, it’s a reminder that PAD does exist in type 2 diabetes, and we need to go looking for it and asking about it. And then now, another medical tool that has been shown to provide functional outcome improvement in our patients and a tool that we’re already familiar with, which, of course, is a GLP-1 receptor agonist. Hello, everyone! My name is Dr Alice Cheng, an endocrinologist from the University of Toronto, and it’s my pleasure to be part of this programme. And I’m going to be speaking to you about peripheral arterial disease and type 2 diabetes, which is probably a topic that we have somewhat forgotten about, to be honest. We spent a lot of time talking about atherosclerotic cardiovascular disease in the context of diabetes, particularly cardiovascular disease, and to some extent cerebrovascular. And then we switched gears and talked a lot about heart failure. But I think now we are refocusing on peripheral arterial disease and reminding ourselves of the importance of PAD in the context of people living with diabetes. It’s estimated that over 230 million people globally have peripheral arterial disease and many of them also live with diabetes, since it is a significant risk factor for the development of peripheral arterial disease. And one of the things that we need to remember as endocrinologists is to be asking about it, which is something that maybe got lost in the focus over the last number of years, because often it’s slow and insidious and people just slowly change what they do from day-to-day and may not even point out the fact that has in fact happened. And they may only bring it up when they have significant intermittent claudication. What did we have to offer people who had peripheral arterial disease to begin with? Well, previously it would be lifestyle modifications, because we know that exercise and physical activity actually improves, reduces symptoms in PAD. Smoking cessation was of course critical, but there were very few, if any, depending on the country you lived in, of actual medical therapy targeting peripheral arterial disease. And it was really surgical intervention and then risk factor modification. Which then brings me to the STRIDE study, which I think is a very important study for people living with diabetes. The STRIDE study was a prospective randomised controlled trial looking at the use of semaglutide, up to 1 mg a week, versus placebo in individuals living with peripheral arterial disease and type 2 diabetes. There were about 800 individuals that were part of this trial. And to get into the study, you had to have type 2 diabetes, but you also had to have symptomatic PAD, specifically Fontaine Class IIa. So, what does that mean? I did not know what that was until I read the study. So, to be Fontaine Class IIa, you have to have symptoms of intermittent claudication but still be able to walk beyond 200 metres. So therefore, in my mind, what that means is it’s a person who has symptomatic PAD but is still functional and not end-stage. And therefore, the kind of person I see in my practise, but also importantly the kind of person you want to intervene, because you can make a difference in that kind of individual. So about 800 people, type 2 diabetes, peripheral arterial disease, randomised to semaglutide 1 mg or placebo. And the outcome of interest was actually a functional outcome. So, it was not “hard outcomes”. It was not amputations or limb ischemia, not powered for that, but functional outcomes. So, a very structured test where there was walking on a treadmill at a 12 % incline at exactly 3.2 kph and measuring how far they could walk and how far pain-free at baseline and then again at 26 weeks and again at 52 weeks and then comparing that ratio of change between the treated group versus the placebo group. Bottom line was it worked. The group that received semaglutide had significantly greater improvement in their maximum walking distance using that structured test at 26 weeks and at 52 weeks actually compared to the placebo group. Now, looking at the ratio graph, I have to admit, I didn’t know what that meant. It was hard for me to contextualise it. So, we were also then given numbers in terms of the mean and the median absolute improvement in pain-free walking distance as well as maximum walking distance. And the number that I have stuck in my head, and there’s other numbers in the paper you can read, is about 39.2 metres, or nearly 40 metres. So, what that meant was that the individuals on semaglutide were able to walk further compared to the placebo group by 40 metres in terms of their maximum walking distance. But that was up an incline, 12 % incline, at 3.2 kph, which to me means that on the flat they could probably have walked even further. Now, 40 metres for some of you may not sound like a lot, but remember, that’s taking something we take for granted, which is walking pain-free, and something that this population was not able to do, and then being able to allow them to do that for further distance. That perhaps means being able to get from your house to the mailbox, or being able to walk farther with your grandkids, or being able to get from the store, back of the store to the front of the store to your car in the parking lot. Things that, again, we’ve taken for granted, but I think has importance to the person living with diabetes. And I think, the other thing I would take away is that risk literacy, which is the ability for people to determine their health risk, is generally low. So, if we tell someone that this intervention will reduce heart attacks, strokes, and death, to us, that’s powerful and that’s meaningful. But for the patient in front of you, that is too abstract of a concept. And I see that in clinical practice that doesn’t always translate and resonate. But yet, if I could say to them, you’re going to be able to walk farther and walk farther with no pain and you’re going to notice that within a short period of time, I actually think that’s going to resonate more for the individual sitting in front of me than me rhyming off statistics on heart attack, strokes and death. One other final piece that I would add is, this adds to the totality of evidence that we have in the GLP-1 space, but it also adds a safety piece to that information, because they actually had the majority of the patients with a BMI below 30 in the study at baseline. So, people that were not necessarily included in some of the traditional GLP-1-based studies. And with all this noise about sarcopenia, that’s a big question that people ask, but yet, these individuals had functional improvement, they walked farther. So, which to me then gives me comfort and confidence that I don’t have to be as worried as much about the sarcopenia piece in this population that would actually be quite vulnerable to sarcopenia and functional decline. So overall, it’s a reminder that PAD does exist in type 2 diabetes, and we need to go looking for it and asking about it. And then now, another medical tool that has been shown to provide functional outcome improvement in our patients, and a tool that we’re already familiar with, which, of course, is a GLP-1 receptor agonist.