GLP-1 RAs and the Evolving Role of Cardiologists in Obesity Management, with Michael Blaha, MD

Michael Blaha, MD
Credit: Johns Hopkins Medicine

The world of obesity management has undergone a plethora of changes since the American Medical Association recognized it as a disease in June 2013. This has included notable advances in best practices and pharmacotherapy. In recent years, the pharmacologic advancement has centered around the weight lowering abilities of the GLP-1 receptor agonist class, namely semaglutide, and the potential of novel dual agonists, such as tirzepatide and retatrutide.¹

On August 8, 2023, Novo Nordisk brought forth the latest potentially paradigm-shifting data in obesity management with the announcement of topline results from the SELECT trial, which examined use of semaglutide 2.4 mg (Wegovy). According to the announcement from Novo Nordisk, the double-blind, placebo-controlled trial, which enrolled adults aged 45 years and older with established cardiovascular disease and overweight or obesity, concluded use of semaglutide 2.4 mg was associated with a 20% statistically significant reduction in risk of major adverse cardiovascular events.²

The announcement of topline results comes 14 months after the agent became the first GLP-1 receptor agonist to receive approval for chronic weight management in adults with overweight or obesity based on data from the STEP program. A group of 4 clinical trials, the SELECT program produced evidence demonstrating use of semaglutide 2.4 mg was associated with a mean reduction in body weight of 17-18%, with this sustained through 68 weeks of use.³

In the August 8, 2023 announcement, the company noted plans to present the data at a conference later this year and also expressed interest in filing for an expanded label indication based off this new data before the close of 2023.²

In a recent interview with Michael Blaha, MD, director of Clinical Research in the Ciccarone Center for the Prevention of Heart Disease at Johns Hopkins Medicine, broke down his perspective on the ideal role of cardiologists in obesity management after leading a discussion on the topic during a session at the American Society of Preventive Cardiology 2023 annual meeting. That conversation with HCPLive Cardiology is the subject of the following Q&A.

Editor’s note: This interview was recorded prior to the announcement of SELECT topline results.

Michael Blaha, MD, on Cardiologists' Role in Obesity Management

HCPLive Cardiology: What is the ideal role of cardiologists in obesity management going forward?

Blaha: There is no doubt that cardiologists must get involved in weight loss management now. The reason is that in the past, we had very ineffective weight loss drugs. We had drugs that were not producing enough weight loss to generate substantial cardiovascular benefits. Upon further study, these drugs commonly failed to offer any cardiovascular advantages.

Currently, we have drugs that can induce weight loss amounts likely to result in cardiovascular benefits. We have, at least for now, an indication for people with diabetes where these same drugs are leading to cardiovascular benefits. It's crucial for cardiologists to pay attention, right? Cardiologists need to be attentive as soon as our outcomes, including heart failure, atrial fibrillation, and atherosclerotic cardiovascular disease, are impacted. This is when our involvement becomes necessary.

I understand why cardiologists weren't involved before, but I also believe that now is the time for cardiologists to become involved due to the new innovations in weight loss. Of course, in the fall, we will hear about the first significant cardiovascular outcomes trial in obesity. This will be the next major test to determine whether cardiologists should become even more involved.

If SELECT yields positive results, I imagine that cardiologists will become even more engaged, and we may potentially have a cardiovascular risk reduction indication for obesity drugs. This appears to be a natural evolution towards more effective drugs that can lower cardiovascular risk. I believe most cardiologists would agree that anything lowering cardiovascular risk falls within our domain. If there is no evidence of cardiovascular risk reduction, as was the case a decade ago, then it lies outside of our domain.

We can engage in an interesting discussion about where it fits in the world of preventive cardiology and in the unique area we call cardiometabolic medicine. Increasingly, cardiologists are establishing cardiometabolic clinics, specialized referral centers for patients with diabetes and obesity requiring comprehensive management. For instance, I run one at Johns Hopkins – a cardiometabolic clinic. We receive referrals from other cardiologists who might feel less comfortable treating diabetes and obesity but acknowledge the necessity to do so. This is the current status of our field.

HCPLive Cardiology: How involved should cardiologists become in obesity management? Should use be emphasized similar to SGLT2 inhibitors or should this be a more limited role?

Blaha: I firmly believe cardiologists should be more engaged, similar to, you know, what you mentioned about SGLT2 inhibitors. So, where do we draw the line? I'd say if someone aims for weight loss but lacks cardiovascular disease or isn't at high risk of cardiovascular disease, that falls outside of a cardiologist's purview.

If someone argues, "We can't treat obesity for everyone," that's valid. I think cardiologists should primarily concentrate on patients at high risk, those likely to gain cardiovascular benefits. For other patients seeking obesity treatment for various reasons, they might seek assistance from other specialists. When we recognize that obesity significantly contributes to cardiovascular disease, as it does in numerous patients, it absolutely becomes a part of a cardiologist's expertise and comfort zone.

At the very least, they should be able to locate or know whom to refer to. For the average cardiologist, they should also feel comfortable in prescribing these medications. I think that the results of SELECT will tell us a lot, assuming that SELECT yields positive results. This domain needs to be within the cardiologist's scope, because we know that obesity drives so much of what we do, particularly AFib, HFpEF, and also ASCVD.

This transcript has been edited for grammar and clarity using artificial intelligence.

References:

1. ^{Campbell P, Iapoce C. 10 years of obesity: A Decade of Advancement and challenges. HCP Live. June 23, 2023. Accessed August 8, 2023. https://www.hcplive.com/view/10-years-of-obesity-a-decade-of-advancement-and-challenges.}
2. ^{Campbell P. Select trial shows semaglutide 2.4 mg could reduce cardiovascular risk. HCP Live. August 8, 2023. Accessed August 8, 2023. https://www.hcplive.com/view/select-trial-shows-semaglutide-2-4-mg-could-reduce-cardiovascular-risk.}
3. ^{Campbell P. Semaglutide (Wegovy) approved for chronic weight management in patients with obesity or overweight. HCP Live. June 4, 2021. Accessed August 8, 2023. https://www.hcplive.com/view/semaglutide-approved-for-chronic-weight-management-in-patients-with-obesity-or-overweight.}