Is long-term use of GLP-1s 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% of U.S. adults are taking GLP-1 medications for weight loss, with some even turning to “gray market” versions of the drug because of accessibility and financial issues.

While these drugs aren’t new, their surge in popularity is. And with much remaining to be known 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 glucagon-like 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 UT Southwestern Medical Center.

“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% 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 some 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?

While GLP-1s aren’t new, there’s a lot that remains unknown about them.

“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.

Looking back at medical treatments quickly adopted at large, there were a handful of cases where we only learned of the side effects when it was too late. Take the thalidomide scandal of the 1960s, for example, in which a drug widely prescribed to treat morning sickness, anxiety and difficulty sleeping in pregnant women wound up causing devastating birth defects. Or hyaluronic acid filler, a cosmetic treatment offered at med spas that is being discovered to expand in size after injection because of its water-loving properties.

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 like 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.

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, said Messiah, 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, said Almandoz, especially so they can perform a risk-benefit ratio and properly 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.”

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