Baku, January 22, AZERTAC

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 issues to Parkinson’s disease, according to Nature. Now, an analysis of data from nearly 2 million people is revealing new 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.

Some researchers say the study lacks enough detail to draw solid conclusions about 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 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 and received funding from companies developing obesity drugs.

Risk assessment

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

“But 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 tracked more than 200,000 people with diabetes 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 may help reduce cravings for tobacco, alcohol, cannabis, and opioids.

But the study found risks associated with the 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.

Data details

Al-Aly speculates that the drugs might influence the risk of so many conditions because they could act on many parts of the body as well as by treating obesity, which contributes to multiple health issues.

“These data are quite valuable,” Seeley says. But he cautions that the study did not match participants for factors such as age and lifestyle, with the treatment being the only difference. Without that, it’s difficult to rule out inherent differences in the groups that could skew the results, he says.

Drucker also notes that the study compared the likelihood of a certain condition between groups over time. This measure can show whether people using GLP-1 drugs are more or less likely to develop that condition compared with people using other diabetes drugs. But health-care providers are interested in knowing the exact number of events in each group to better understand how relevant the results are for their patients, he says.

For example, a two-fold reduction in the risk of a certain condition would be significant if it decreased from 350 to 175 cases, but if the reduction were from 10 to 5 cases, it would have little clinical relevance, Drucker says. “I can’t tell from the way the data is presented what the absolute events are for some of these really interesting events,” he says.

Al-Aly says that future studies will focus on these numbers for specific diseases. Because the current work mainly involves older, white men linked to the US Department of Veterans Affairs, studies in diverse groups will also be important to confirm the findings, he says.