Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

The more GLP-1s catch on, the more benefits researchers discover. Originally formulated to treat diabetes, the popular weight-loss drugs have been shown to improve kidney health, liver function, cardiovascular disease, arthritis, and even dementia and addiction.

What happens when you stop taking them, though? We know the weight tends to return, but research published today in BMJ Medicine shows some of the other benefits of GLP-1s vanish as well.

“There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop,” study author Ziyad Al-Aly of Washington University in St. Louis said in a statement.

To find out what happens when people stop taking GLP-1s, Al-Aly’s team of researchers tracked the health of more than 333,000 United States veterans with type 2 diabetes for three years. They found that the risk of heart attack and stroke jumped in those that paused GLP-1 treatments for as little as six months, compared to those who continued taking the medication. The longer time spent off GLP-1s, the greater the risk of major cardiovascular events—up to 22 percent for those who abstained for two years.

“When they stop, it’s not just weight that comes back; they experience a resurgence in inflammation, blood pressure, and cholesterol,” Al-Aly explained. “Weight regain is visible; the metabolic reversal is not.”

What about those who restarted a GLP-1 regimen after taking a break? Unfortunately, the benefits didn’t fully return. Participants who stuck with GLP-1s for the entire three-year study period saw their risk of heart attack and stroke cut by 18 percent while those who restarted after a break saw only a 12 percent reduction. Researchers say this is because the benefits of GLP-1s take time to fully accumulate, but then vanish quickly without the drug.

“Our data suggest this metabolic whiplash is detrimental to heart health,” Al-Aly added. “Restarting the medication helped restore some protection, but only partially, showing that discontinuation leaves a lasting scar.”

Such whiplash could mean many people are in for a rude awakening. Research shows that around half of people who start GLP-1s quit taking the medication after only a short period. To Al-Aly, the solution is a shift in mindset around GLP-1 treatment and more candid conversations about side effects.

“Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right—not an afterthought,” Al-Aly said. “Health systems need plans in place to help people continue their medication indefinitely, recognizing that GLP-1s treat chronic conditions.”

GLP-1s have life-changing effects, but taking them could be a lifelong commitment.