GLP-1 medication has helped millions of Americans lose pounds in recent years, but a new study from Veterans Affairs shows quitting the drug could pose health risks, along with packing the weight back on.
The study included more than 330,000 VA patients, discovering that those who stopped using GLP-1s, such as Ozempic, had a 22% increase in cardiovascular problems, leading to strokes and heart failure.
Researchers also noted that while long-term usage of GLP-1 medication is typically needed to maintain a healthy weight and decrease obesity risk factors, insurance coverage and affordability haven’t met the demand for these drugs.
Dr. Ziyad Al-Aly serves as director of the Clinical Epidemiology Center at the VA Saint Louis Health Care System. As a scientist, Al-Aly is also chief of Research and Development at the VA facility. He questioned what would happen to the heart when a patient stopped using weight loss drugs, which led to the recent study, published in BMJ Medicine.
“We examined a question that hasn’t received nearly enough attention: What are the cardiovascular consequences of stopping GLP-1 drugs?” Al-Aly posted on LinkedIn.
Benefits and Side Effects
It may seem hard to believe, but GLP-1 weight loss drugs have been around since 2005, when the Food and Drug Administration (FDA) approved Exenatide to treat Type 2 diabetes. However, it wasn’t until 2021, when Ozempic and Wegovy hit the market, that the medication skyrocketed in popularity.
According to Al-Aly, an estimated 1 in 8 adults in the U.S. has used a GLP-1, with 36 to 81 percent ditching the drugs within the first year, either due to meeting their weight-loss goals, high cost, or concern over side effects. Patients who quit tend to gain back the weight, but Al-Aly also wanted to examine how this affects the heart.
“Using VA healthcare records, we emulated a randomized trial following more than 333,000 adults with type 2 diabetes for up to three years, testing 16 different treatment scenarios — continuous use, discontinuation at various time points, interruption, and restart,” Al-Aly said.
The VA’s study found that cardiovascular protection builds progressively while using the medication. Bottom line – using GLP-1s can reduce the risk of heart disease and stroke significantly within a few years.
“Three years of continuous GLP-1 use produced an 18% reduction in major adverse cardiovascular events, heart attack, stroke, and death,” Al-Aly said. “But that protection erodes quickly. Stopping for just six months was tied to a 4% increase in cardiovascular risk. One year off: 14%. Two years off: 22%.”
Most surprisingly, the study showed that patients who quit the drug for several months, then continued using it again, couldn’t recoup the benefits they gained when they were on the medication.
“Restarting helped — it closed some of the gap — but did not fully restore the protection of uninterrupted use,” Al-Aly said. “Discontinuation leaves a lasting scar.”
Risks of Quitting the Drugs
Along with re-gaining weight, patients also experienced a spike in inflammation, blood pressure, cholesterol, and resistance to insulin.
“Weight regain is visible. The metabolic reversal is not,” Al-Aly said. “We think of this as a form of metabolic whiplash, and our data suggest it is detrimental to heart health.”
The study also shines light on the affordability, and lack of insurance coverage, for weight-loss drugs. Through the VA healthcare system, insurance copays are capped at $11 per month, according to Al-Aly. Even with VA coverage, and lower costs, more than 25% of patients stopped using the drug altogether, and another 25% halted treatment for a short time.
While cost is a factor, Al-Aly highlighted other concerns that prevent more patients from using the medication, such as side effects, patients' thinking the medication will not help them lose weight, and drug shortages. The popularity and success of GLP-1s have pressured manufacturers to stock their shelves.
“The implications are clear: clinicians should treat persistence as a clinical outcome in its own right,” Al-Aly said. “Health systems need to identify and support patients at risk of stopping. And policymakers need to address the barriers, financial and otherwise, that make continuous treatment unsustainable for many. The data show a clear dose-response: the more consistently people stay on, the greater the heart protection.”
And as the study shows, stopping can unravel years of cardiovascular benefits.
