Heart Health Implications of GLP-1 Medications

A significant advantage of GLP-1 injections is their ability to greatly decrease the risk of heart attacks, strokes, and other cardiovascular issues.

However, the moment patients cease their medication, those heart benefits tend to vanish.

A recent extensive study indicates that heart risks can start to arise within just six months after discontinuation and may nearly return to pre-treatment levels within a year and a half.

The researchers noted that stopping the medication might create something akin to “metabolic whiplash.”

According to Dr. Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis, the reversal of these heart benefits happens faster than the time it took to initially gain them.

“Building up those benefits takes a long time, but losing them seems much quicker,” he explained. He also noted that it took three years to achieve cardiovascular benefits that could be undone in just a year and a half after stopping the drugs.

This study, published in BMJ Medicine, emphasizes the necessity of continuous GLP-1 treatment to retain its benefits.

Researchers examined the medical records of over 333,000 type 2 diabetes patients treated through the Veterans Health Administration.

It’s essential to note that this research did not account for individuals using similar medications primarily for weight loss, which is a common reason for GLP-1 use in the U.S.

The study specifically compared around 132,000 patients on GLP-1 medications with over 201,000 others who received a different type of diabetes medication known as sulfonylureas.

The medications in the study included both newer GLP-1s, like semaglutide (Ozempic) and tirzepatide (Mounjaro), and older versions such as liraglutide (Victoza), exenatide (Byetta, Bydureon BCise), and dulaglutide (Trulicity).

Participants who consistently took GLP-1s for an average of three years experienced significant heart health improvements, resulting in an 18% lower risk of heart attacks, strokes, or death compared to those on sulfonylureas.

Among GLP-1 users, a further examination showed that individuals who stopped taking the medication faced rising heart risks shortly after discontinuation.

Compared to those who continued their treatment, those who stopped saw heart risks increase by 4% six months later, 14% after a year, and 22% by the second year post-medication, effectively erasing earlier benefits.

This observed benefit closely mirrors findings from another study, the SELECT trial, which assessed heart event reductions in individuals taking semaglutide for obesity. That study found a roughly 20% decrease in serious cardiovascular events compared to a placebo group.

Interestingly, the SELECT study also revealed that individuals experienced heart benefits from semaglutide even without weight loss, according to Dr. Melanie Jay from NYU Langone’s Comprehensive Program on Obesity.

“This suggests there are both weight-dependent and weight-independent mechanisms at play for heart health,” she indicated.

While the exact reasons GLP-1 medications improve cardiovascular health remain unclear, weight loss—often associated with these drugs—might reduce inflammation, which can positively affect the heart. Additionally, since the heart has GLP-1 receptors, a direct influence of the medication on heart tissue is plausible.

Dr. Jay pointed out that this study is one of the largest to confirm that the heart benefits of GLP-1 medications diminish after stopping treatment. She commended the study’s design that utilized a vast, detailed patient database.

“It doesn’t mean you’re worse off than if you’d never taken it; you’re just in a worse position than if you had remained on it,” she clarified.

A significant number of patients do stop GLP-1 medications, with studies suggesting that about half discontinue use within a year. Common reasons for this include side effects such as nausea and fatigue, alongside costs, as many who stop cite financial barriers to continued use.

Despite the strong findings, some questions linger. For instance, it’s uncertain whether individuals who discontinue but maintain their weight loss might continue to experience cardiovascular benefits. There’s also the question of whether maintenance dosing could help prevent the decline in heart health.

“We know maintaining a lower dose or infrequent dosing matters, but we don’t yet know about its impact on cardiovascular benefits,” she noted.

What seems straightforward is the importance of remaining on the medication for heart health goals.

“This is likely a long-term necessity,” emphasized Dr. Al-Aly.

He expressed understanding about challenges, especially when patients lose insurance coverage for these medications after achieving weight loss.

He urged insurers to recognize the evolving evidence showing that continuous use is crucial for maximizing benefits.

“Discontinuation has serious implications for heart health,” he warned. “Denying access to these medications puts people at unnecessary risk.”