In recent years, the popularity of weight-loss drugs like Ozempic and Wegovy has soared so dramatically that they’ve inspired new vocabulary, spurred global shortages, and prompted moral debates. Prescription growth hit 13% in just three months, with 2 million Americans now using the drug. Marketed as “miracle drugs,” these medications, part of a class called GLP-1 receptor agonists, have transformed how doctors treat diabetes, obesity, and even addiction.

But as millions jump the GLP-1 drug bandwagon, the scale of these drugs’ side effects has become increasingly apparent.

Using data from over two million patients, scientists at the Washington University School of Medicine and the Veterans Affairs St. Louis Health Care System have built what they call an “atlas” of the drugs’ effects on the human body. The study is one of the most comprehensive investigations yet into GLP-1 drugs, tracking 175 health outcomes across all major organ systems.

“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems,” said Dr. Ziyad Al-Aly, the study’s senior author and a clinical epidemiologist.

Potential Benefits

GLP-1 drugs like semaglutide (the active ingredient in Ozempic and Wegovy) were originally designed to mimic hormones that stimulate insulin release, helping patients with type 2 diabetes. But they quickly became famous for their ability to trigger significant weight loss by suppressing appetite and slowing digestion.

Clinical trials showed cardiovascular benefits and improved kidney function. But many of those trials only monitored patients for a few months and tested a narrow range of outcomes.

Al-Aly’s team wanted to take a broader view.

So, they pulled anonymized data from the U.S. Department of Veterans Affairs, focusing on 215,970 people who started taking GLP-1 drugs between 2017 and 2023. They compared their health outcomes to those of over a million people using other diabetes medications or receiving standard care.

Compared to standard care, GLP-1 drugs were associated with a lower risk of 42 different conditions, including heart attacks, strokes, kidney failure, respiratory infections, and even Alzheimer’s disease. The drugs also appeared to reduce substance use disorders — including alcohol, cannabis, opioids, and stimulants — and even cut the risk of suicide attempts.

The effect sizes were modest, often ranging between 10% and 20% risk reductions. But across such a wide array of conditions, the cumulative impact could be substantial.

“These drugs act on receptors throughout the brain and body,” said Al-Aly. “That might explain why we’re seeing effects far beyond blood sugar or weight.”

Animal studies support that theory. GLP-1 drugs reduce inflammation in the brain and interfere with reward pathways linked to addiction. Human data from the new study suggests they also lower the risk of seizures, bulimia, schizophrenia, and suicidal behavior.

“There’s a growing body of research suggesting GLP-1 drugs might serve as adjuvants for treating neuropsychiatric conditions,” the authors wrote.

And they’re not alone in this speculation. Other researchers are already exploring whether these drugs might be used to treat addiction or even prevent cognitive decline in aging populations.

But Not Without Risks

Still, no medicine that touches so many systems can do so without consequences.

The study found an increased risk for 19 outcomes, some of them serious.

Users had higher rates of gastrointestinal problems like nausea, vomiting, GERD (acid reflux), and abdominal pain. More worryingly, they were also more likely to suffer from pancreatitis (a painful and potentially fatal inflammation of the pancreas), kidney stones, and kidney inflammation. The risk of acute drug-induced pancreatitis was more than twice that of non-users.

Vision changes and other musculoskeletal issues, like arthritis and tendinitis, were also noted. Sleep disturbances, syncope (fainting), and headaches were among the subtler but still significant concerns.

These side effects aren’t entirely new. Reports of nausea and “Ozempic face” — a term coined for the rapid facial fat loss some users experience — have circulated for years. But this is the first time such a large and systematic evaluation has mapped the full scope of possible risks.

“Rarer side effects may emerge as more patients take these medicines in clinical practice,” explained Penny Ward, a physician at King’s College London. “This is why we continue to monitor the safety of medicines on the market.”

In the UK, regulators have linked at least ten deaths to GLP-1-related pancreatitis. And while side effects like NAION (a rare optic nerve condition that can cause blindness) remain uncommon, studies now suggest a fourfold increase in risk among diabetic users.

A Balancing Act

Despite the concerns, researchers aren’t calling for restrictions.

“The list of benefits for this drug, if taken as prescribed, is still significantly longer and more impactful than risks,” Karolina Skibicka, a neuroendocrinologist at the University of Calgary, told DW.

But she added an important caveat: “We need studies which include women. Women show unique side-effects to many pharmacotherapies, and still in most studies women are often underrepresented at various stages of testing.”

That’s a known limitation of the current study, which was conducted using VA health records, a system whose patient base is disproportionately male. Only about 5% of participants were women.

And that may not be the only blind spot. Because the drugs are increasingly used for obesity rather than diabetes, the dosages and durations are often higher and longer than in original trials. “More data is needed about those taking the drug for obesity,” Skibicka said.

Al-Aly agrees. He emphasizes that the findings should not discourage use but instead guide safer prescriptions and spur targeted research.

“GLP-1RA drugs can have broad health benefits,” he said. “However, they are not without risks. Our findings underscore the possibility for wider applications for these medications but also highlight important risks that should be carefully monitored.”

Where Do We Go from Here?

For now, the drugs are here to stay. One in eight U.S. adults has already taken a GLP-1 drug at least once, and demand continues to grow globally.

But the new atlas of side effects and benefits offers a way forward not just for better prescribing practices, but for understanding the full biological reach of a molecule originally intended to control blood sugar.

As more data emerges, that insight might help scientists repurpose GLP-1 drugs in ways we’re only beginning to imagine.

After all, a molecule that reshapes the risk of Alzheimer’s, addiction, and cardiovascular disease, all at once? That’s not something we can afford to easily ignore.

The findings appeared in the journal Nature Medicine.