Blockbuster obesity drugs such as Ozempic have been celebrated for their ability to treat weight loss and a surprising range of other conditions, from heart problems to Parkinson’s disease. Now, an analysis of data from nearly 2 million people is revealing insights into the effects of these medications — including the risks they pose.

The findings, published in Nature Medicine on 20 January¹, confirm that these drugs, called glucagon-like peptide 1 (GLP-1) receptor agonists, offer more than just weight-loss benefits. But the work highlights newly recognized risks of the medicines, including an increased likelihood of developing arthritis and a potentially deadly condition called pancreatitis.

New obesity definition sidelines BMI to focus on health

Some researchers say that the study lacks enough detail to draw solid conclusions about the drugs’ benefits and risks. “It is one thing for a benefit or harm to be ‘associated’ with use of GLP-1, it is another thing if it changes the risk a great deal,” says Randy Seeley, an obesity specialist at the University of Michigan Medical School in Ann Arbor, who wasn’t involved in the research.

“Nevertheless, I think this is the kind of data that will help guide real-world use of these drugs,” says Seeley, who has consulted for and received funding from companies developing obesity drugs.

Risk assessment

The study focused on GLP-1 receptor agonists, including semaglutide, which is sold as Ozempic to treat diabetes and is now widely prescribed for weight loss.

“No one had comprehensively investigated the effectiveness and risks of GLP-1 receptor agonists across all possible health outcomes,” says Ziyad Al-Aly, a physician-scientist at the Veterans Affairs St. Louis Health Care System in Missouri, who led the work.

Over about 3.5 years, Al-Aly and his colleagues followed more than 200,000 people with diabetes who were on GLP-1 drugs and about 1.7 million people with diabetes using other blood-sugar-lowering medications. They tracked the effects of GLP-1 drugs on 175 health conditions.

Compared with other diabetes medications, GLP-1 drugs were linked to a lower risk of dozens of conditions, including heart disease, stroke and kidney disease. They also lowered the risk of psychotic disorders by 18%, Alzheimer’s disease by 12% and addiction disorders by an average of 13%.

“What stood out to me is a consistent effect on addiction disorders,” Al-Aly says. Because GLP-1 drugs act on brain regions involved in reward and impulse control, he adds, they might help to reduce cravings for tobacco, alcohol, cannabis and opioids.

But the study found risks associated with GLP-1 use. For example, these drugs were associated with an 11% increase in arthritis risk and a 146% higher risk of pancreatitis — an inflammation of the pancreas that can lead to life-threatening complications. These are newly highlighted risks, says Daniel Drucker, an endocrinologist at the University of Toronto in Canada.