Sweeping review looks at effect of weight-loss drugs on 175 conditions

A study by the Department of Veterans Affairs on the relationship between GLP-1 weight-loss drugs and 175 diseases and conditions supports a lot of what scientists already suspected about potential benefits, but contains a few surprises, too.

The findings, published Monday in the journal Nature Medicine and based on an analysis of medical records from about 2.5 million patients in the VA system, support the idea that the medications might be able to help patients with Alzheimer’s disease and who are suffering from substance abuse involving alcohol, cannabis and narcotics. The “discovery” analysis of the drugs involves delving into data to look for connections and is not meant to establish causal relationships, but instead to generate hypotheses.

The research is the first to attempt to comprehensively investigate the impact—both good and bad—of the drugs on the human body. It arrives at a time when anecdotal reports and small studies attesting to new effects of drugs sold under brand names such as Mounjaro, Ozempic, Wegovy and Zepbound emerge regularly.

Mounjaro and Zepbound are both made by Indianapolis-based Eli Lilly and Co.

“We tend to think of drugs as surgically designed to do only one thing. But the reality is almost never like this,” Ziyad Al-Aly, a co-author of the paper and chief of research for the VA St. Louis Health Care System, said at a news briefing. In fact, Al-Aly said many medications result in an “intricate web of various effects.”

Usage of GLP-1 medications has exploded in recent years, rewriting the conversation around health and body image. The shots’ exorbitant price—roughly $1,000 a month—and spotty insurance coverage have raised uncomfortable questions about access and equity.

Novo Nordisk’s Ozempic is approved by the Food and Drug Administration to treat diabetes, obesity and cardiac risk. The company has said it intends to apply to update the drug’s label for use in patients with chronic kidney disease.

About 1 in 8 U.S. adults said they had tried or are using GLP-1 medications, according to a May 2024 poll by KFF, a nonpartisan health-care research organization.

Nora Volkow, director of the National Institute on Drug Abuse, called the findings fascinating and said the study “forces us to see that looking at a medicine in a comprehensive fashion could be very valuable and help advance the way we do medicine overall.”

The research compared diabetes patients on Ozempic and other GLP-1 drugs with people taking older treatments. The study also included subjects known as controls who did not have diabetes.

David Cummings, professor of medicine in the division of metabolism, endocrinology and nutrition at the University of Washington, said he likes to think of database dives such as this as fishing expeditions. Cast a wide net, and you probably get some statistical blips that end up having no meaning even as you get some telling hits.

“The surprising ones are cool because that gives you a new avenue to pursue,” he said.

Among the expected results: GLP-1 was associated with lower risk of cardiovascular, kidney and liver issues. On the negative side, it was linked to gastrointestinal issues such as reflux, headaches and pancreatitis.

Some unexpected findings include a suggestion that the drugs could help with blood clotting, respiration, and infection.

“Those are very new, and I’d like to see more research there,” said Fatima Cody Stanford, an obesity medicine physician at Massachusetts General Hospital and an associate professor at Harvard Medical School.

The data also appeared to support recent studies that found suicidal thoughts were reduced by GLP-1 drugs rather than increasing them as feared early on. Volkow said the signals suggesting a reduction in suicidality should be followed up, and wondered if it might indicate that GLP-1 drugs dampen people’s stress responses, a finding in animal models.

The NIH had been studying the impact of GLP-1 drugs on substance abuse even before the arrival of Ozempic, and Volkow said some clinicians have been prescribing them off-label already.

“The evidence is suggestive absolutely, but it’s not at the standard to very clearly say. ‘Let’s recommend this for a treatment’,” Volkow said.

Some scientists were puzzled by an increased signal of arthritis among patients taking the drugs. Cummings called that “very strange” because weight loss should ease arthritis symptoms.

Stanford cautioned that the study should be viewed within the context of the VA population, which tends to be older, less diverse and more male than the U.S. population as a whole. Because of their age, she said, the patients studied are likely to have multiple health conditions and be on multiple medications, which may have affected results.

The overarching takeaway for Cummings is that there were no new red flags in the data that should make people worry about GLP-1 drugs. To the contrary, he said, “every medicine has its pluses and minuses, and these are no exception. But in this case, the pluses greatly outweigh the negative.”