I'm Dr Steven Nissen and I am the Chief Academic Officer of the Heart, Vascular and Thoracic Institute at the Cleveland Clinic.

How do you determine which CVD patients are appropriate candidates for GLP-1 RAs or other weight management therapies?

Well, we know, and we've known for quite some time that obesity is a very strong risk factor for multiple cardiovascular abnormalities. The question of course, is at what level of obesity should we treat with the drugs? Many of the clinical trials have gone down to as low as a BMI of 27. Although most third-party payers are really not going to approve payment for these drugs unless the BMI is over 30.

Probably BMI is not the best measure. The best measure would be a combination of BMI, yes, but waist circumference is very important because it's intra-abdominal fat that seems to drive cardiovascular risk. And of course, the level of cardiovascular risk for the patient is important. If a patient has had a prior event, then they're more likely to benefit from treatment. But we also think there's probably going to be evidence in the next several years that people that have never had a cardiovascular event will benefit from a GLP1 agonist. And then of course, people with diabetes are particularly good candidates because these drugs not only reduce body weight, they help to control blood sugar and will reduce hemoglobin A1C substantially.

What is your approach to setting realistic weight loss goals to achieve long-term CV benefits?

Well, of course, we don't know. We have some evidence from some trials that suggests that, you know, you need pretty substantial weight loss. So I would say that it's not so much the target as it is the extent of weight loss.

We've done some studies with bariatric surgery that suggest that you need, you know, 10 to 15% body weight decrease in most people to see the cardiovascular benefits. So for me, it's really targeting how much weight to lose. Now, if someone's 350 pounds or has a BMI of 40, then 10% or 15% weight loss, they're still going to be obese. But interestingly enough, there appears to be quite substantial benefits even in those people. A normal body weight is a good thing and if we get there, that's obviously important for patients. But if we can't, then trying to get at least a 10 or even a 15% weight loss makes sense.

How would you collaborate with primary care, cardiology, and bariatric specialists?

Well, for these patients, everybody has to work together. Here at the Cleveland Clinic, we have a bariatric treatment group that includes both medical treatment experts and surgeons. We have a very good surgical team. And in some people, bariatric surgery is going to be a better option, particularly the patient I just talked about that has a BMI of 40. They're probably not going to get to where they need to be with just a GLP1 agonist. So we all have to collaborate.

One of the important things for primary care physicians is to realize that diet and lifestyle changes tend to be relatively ineffective at weight loss. I wish that weren't true, but we've studied this and others have studied it and unfortunately this is a disorder that requires interventions. Those interventions need to represent a collaboration between the primary care physician, the medical weight loss specialists, the cardiologists and the bariatric surgeons. And together we need to choose the best option for each patient.

What clinical outcomes do you use to measure the success of weight management interventions in CVD care, both in the short and long term?

Obviously, we want to prevent events and so the patients that lose weight and don't have a cardiovascular event, that's a win, that's a success. But there are other biochemical measures, certainly hemoglobin A1C. Many of these patients are either diabetic or prediabetic and they will, in some cases with substantial weight loss, revert to a non-diabetes status. And that's obviously a very big win.

Blood pressure is another measure of success. Weight loss is very effective at reducing blood pressure. And some of these patients will be on two or three or even four antihypertensive drugs. And the ability to withdraw some of those drugs, in a few cases, even all of them, is a huge advantage. The ability to, with weight loss, withdraw other glucose lowering therapies is another huge advantage. So weight loss can drive a lot of benefits and they can be measured. And of course the whole goal of this is to prevent cardiovascular events.

What strategies do you use to improve treatment adherence?

Well, first of all, you have to educate patients. They have to understand several things. One is that there are adverse effects of GLP1 and GIP agonists. And by the way, you know, we're not limited now just to a GLP1 agonist, we have drugs like tirzepatide, which is a GLP1 GIP agonist, which seems to be somewhat more effective. And that also relates to the strategy that people that need a lot of weight loss are going to lose more weight with tirzepatide than say a GLP1 agonist like semaglutide. So that's important thing for people to know.

But for both types of drugs, early on there's some nausea, some people even have vomiting or other gastrointestinal adverse effects. I tell them to expect those effects, that over time they tend to lessen substantially and if they can stay on treatment, we can get them to an effective dose over time. If they do have adverse effects, I also tell them that there's an opportunity to back titrate the medications to a lower dose. And so patient education here is very important. Like everything in medicine, drugs have both favorable and adverse effects. If people know about them, then it's a lot easier to manage.