GLP-1s and Cardiovascular Risk: What the Latest Evidence Reveals

Bret: 
Welcome to the Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a non-profit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies, such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only and we aren’t giving medical advice, we hope you will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health

GLP-1 medications, like semaglutide and others, are being called game changers, not just for weight loss, but also for heart health. And the data seem to support that claim. But here’s the secret. They only work if you stay on them seemingly forever. Now, is that a reasonable thing to expect? I don’t think so.

Let’s talk about it. So, we’ll start with the benefits. In large clinical trials, GLP-1 receptor agonists, like semaglutide, Wegovy, Ozempic, Mounjaro, and others, they reduce the risk of major cardiovascular events, things like heart attack, stroke, cardiovascular death, by about 15 to 20%. Now, that’s the relative risk reduction over five years.

That equates to about a one and a half to 2% absolute risk reduction, which ranks pretty highly among medication effects. So, it’s easy to look at these results and conclude these medications are great. Maybe they’re the solution to our metabolic health epidemic? But here’s the question we don’t talk about enough. What happens when people stop taking these drugs?

And that’s a crucial question. Because in the real world, many people don’t stay on them long-term, with one-half to two-thirds of people stopping within a year. A new study now published in BMJ Medicine adds light to the question about what happens after we stop GLP-1s, and it’s not very encouraging.

In one large real-world cohort, over 300,000 patients, those continuously taking GLP-1 medications had about an 18% lower risk of heart attack, stroke, or death compared to other treatments, like sulfonylureas. Now, that’s the good news. But interestingly, if someone took a GLP-1 for 18 months or less, it appears as if there was no cardiac benefit.

As one author stated, “It’s as if they never took the drug at all.” So, it takes more than 18 months on a GLP-1 to see significant cardiac benefits. But here’s the catch. All of those benefits start to retreat within six months of stopping the drug. And they’re essentially eliminated within 18 months of stopping it.

So again, it’s as if they never took the drug. So, the cardiovascular protection doesn’t persist when the medication is stopped, which really should not be a surprise. We shouldn’t need a study to tell us that because it makes sense. The medications, they’re effective, but they’re not fixing the underlying problem.

They’re only temporarily managing it, and this study reinforces that. These medications can help you lose weight and can temporarily improve your metabolic health. But they don’t change long-term eating patterns. They don’t change your physical fitness, your metabolic flexibility, or many of the underlying drivers of cardiovascular disease and certainly cardiometabolic disease.

And I think this is the key insight from the paper. If the underlying lifestyle and metabolic drivers don’t change, then once the medication’s removed, the risk comes back. And interestingly, this study was in a VA population. So basically, the cost was not an issue at all for adherence. So, the discontinue rate may be even higher in a population that has a higher copay, where cost could be an issue.

So, it could be even more impactful with reduction of the cardiovascular risk, elimination of the cardiovascular risk. But it’s fascinating to watch the reaction on this paper. So. One author on Twitter said, “That’s okay. These drugs are lifelong interventions.” And he said it as if it’s perfectly acceptable, right?

As if we should expect to stay on the medication forever to lower our cardiovascular event risk. As if there’s little downside to committing someone to a lifetime dependence on medications with cost and side effects. So, I think we need to ask, does it have to be this way, or can we use these medications as aids to help find sustainable interventions that actually address the underlying causes without the costs and side effects?

I think we should see GLP-1s as a very powerful short-term tool. A tool that can trigger weight loss, improve short-term metabolic health, and subsequent cardiac risk, that can help people break free from food noise and constant hunger. When someone has spent years struggling with overweight and obesity, diabetes, metabolic disease, making lifestyle changes can feel overwhelming or almost impossible at times, and GLP-1s can help with that.

But if you rely on the medication alone, the studies and real-world experience clearly show the weight returns. The metabolic markers worsen, and the cardiovascular risk increases. It’s as if they never had the brief benefits in the first place. That’s why it’s imperative for everyone who’s going to start a GLP-1 and for every doctor who’s going to prescribe a GLP-1 to also use that time to build sustainable nutrition habits with ample protein, low refined carbohydrates, and long-term physical activity that helps maintain muscle mass and helping them prioritize their long-term metabolic health.

This doesn’t mean GLP-1s shouldn’t be used long-term in some patients. For some high-risk people, it makes sense. But committing millions and millions of people to a lifetime dependence on the medication or face a return of poor health isn’t optimal medical care, and doctors need to realize that. If we want the benefits to last, we need to pair these medications with meaningful long-term lifestyle changes that improve metabolic health, address hunger, maintain muscle mass, and leave us feeling great physically and mentally.

Because the goal isn’t just to lower risk temporarily. The goal is to restore our lives and build lasting cardiovascular, metabolic mental health. These medications aren’t going away. In fact, they’re only becoming more and more prevalent. That’s why the time is now to ensure proper stewardship and appropriate use.

That’s why the Coalition for Metabolic Health recently formed a GLP-1 task force, and I encourage you to check out their position paper at coalitionformetabolichealth.org. It’s clear that individuals and clinicians need to take responsibility for proper use of this medication.

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