Is long-term use of GLP-1 weight-loss drugs safe?

GLP-1s seem to be quickly becoming the “wonder drug” of the 21st century.

In the past few years, these drugs have permeated news feeds, social media and even day-to-day conversations. It is now estimated that around 11 percent of U.S. adults are taking GLP-1 medications for weight loss, with some even turning to “gray market” versions of the drugs because of accessibility and financial issues.

While these drugs aren’t new, their surge in popularity is. And with much still unknown about the effects of long-term GLP-1 use, it raises the question: Could these so-called wonder drugs be too good to be true?

What are GLP-1s?

GLP-1s, or glucagonlike peptide-1s, are synthesized versions of a hormone that helps control blood sugars and, when you’re eating, lets you know when you are full, said Dr. Jaime Almandoz, a professor of internal medicine and the medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center in Dallas.

“Essentially, they make us satisfied with less food for longer,” Almandoz said, making GLP-1s a revolutionary treatment for Type 2 diabetes and for helping with chronic weight management.

The first GLP-1 drug was approved by the Food and Drug Administration as a Type 2 diabetes treatment in 2005, and the first GLP-1 drug for weight loss was approved nine years later.

Many large clinical trials show robust benefits beyond weight loss, Almandoz said. The 2023 SELECT study, he noted, reported a 20 percent average reduction in the risk of heart attacks, strokes and other major cardiovascular events among obese participants while taking the GLP-1 semaglutide.

Some research suggests GLP-1s could provide relief from substance-use disorders or cravings, said Sarah Messiah, the associate dean for research and director of the Child and Adolescent Population Health Program at UT Southwestern.

“GLP-1s seem to have a general effect on reward processes in general,” Messiah said. “It’s not specific to food. People are also anecdotally seeing changes in the way it’s making them respond to other substances, like alcohol.”

What don’t we know

“I do think it is appropriate to ask, what are we going to learn with much longer-term use? And how do we make sure these medications are being used appropriately?” Almandoz said.

Some research has been conducted on the long-term effectiveness and safety of GLP-1 usage. Studies published between 2018 and 2025 showed sustained weight loss and blood sugar control over 40- to 120-week periods, but some participants did experience gastrointestinal side effects such as nausea, vomiting and diarrhea.

“If you don’t need it, you probably won’t get the same benefits, and you might be putting yourself at risk for potential side effects,” Messiah said. The side effects aren’t limited to gastrointestinal issues and can include pancreatitis, acute kidney injury and thyroid cancer.

Additional concerns

Other major points of concern, Almandoz said, are supply shortages, insurance issues and high out-of-pocket costs that can restrict access to GLP-1s for those who would benefit the most from them. A study conducted by Cleveland Clinic last year found almost half of patients who discontinued use of GLP-1s did so because of financial reasons. According to the University of Chicago Medicine, GLP-1s can cost roughly $700 to $800 per month.

This can cause patients to turn to cheaper “gray market” alternatives, Messiah said, referring to risky, off-market drugs not approved by the Food and Drug Administration. These nonprescription drugs might appear attractive to people who don’t necessarily have medical needs for GLP-1s.

It’s important to see a healthcare professional who is well-versed on GLP-1s before starting them, Almandoz said, so they can weigh the risks and benefits and advise whether GLP-1 usage is appropriate.

GLP-1s shouldn’t be treated as a silver bullet, either. Almandoz emphasized the importance of using the drugs as a co-therapy, pointing toward making lifestyle changes in diet and exercise to ensure positive health outcomes.

“We need to make sure we are focusing on health outcomes,” Almandoz said, “and not just trying to get the lowest number on the scale possible.”