GLP-1 use for weight loss has grown in popularity over the past few years with many clinical trials reporting the drugs are safe for use. A report released in January 2026 found that caution needs to be used when prescribing the medication, pointing out that patients should have regular oversight, monitoring and coordinated clinical care.
In the report, written by Ariana Chao, Adam Gilden and Thomas Wadden, published in PLoS Med, when GLP-1s are prescribed for weight loss, there is a risk of side effects, long-term outcomes and the use of products that may be unregulated. The study points out that the drugs were initially developed for the management of Type 2 diabetes, but one of the side effects of the drugs was weight loss, leading doctors to prescribe them for obesity.
“Interest in these medications from healthcare professionals and the public has been unprecedented, with an estimated 700 percent increase in GLP-1 prescriptions among people without diabetes from 2019 to 2023,” the report reads. “This upsurge has been fueled by robust clinical trial efficacy data, favorable aspects on metabolism and obesity-related complications, growth in recognition of obesity as a chronic medical disease and pervasive media exposure.”
The rapid expansion of use raised important questions regarding safety, according to the researchers. The study found that there have been more than 40 clinical trials of GLP-1 based medications related to the treatment of obesity. The studies have included a wide range of populations, including those with Type-2 diabetes, cardiovascular disease, congestive heart failure, obstructive sleep apnea and chronic kidney disease.
“In phase 3 trials, the most common adverse events have been gastrointestinal, including nausea, vomiting, diarrhea, constipation, bloating and abdominal pain,” the report reads. “These effects tend to be mild; are most pronounced during dose escalation and occur in up to half of patients. Other side effects include fatigue, headache and dyspepsia. Rare, but serious, side effects have included cholelithiasis, pancreatitis and acute kidney injury, which are noted on the prescribing information.”
Because clinical trials often have strict inclusion and exclusion criteria as well as short follow-up durations, adverse events may not be captured quickly. Often, studies exclude individuals with a history of an eating disorder, history of bariatric surgery, active suicidal ideation, major depression or other significant mental illness, severe gastrointestinal disease or a history of pancreatitis. This means that drug safety among individuals with those conditions are lacking.
“Drug interactions also must be carefully considered,” the report found. “Delayed gastric emptying can reduce absorption of oral contraceptives, diminishing their effectiveness whiel us of GLP-1s with insulin or sulfonylureas increase the risk of hypoglycemia. The rapid expansion of GLP-1 prescribing has outpaced the evidence in in some areas.”
Another negative aspect of GLP-1 use is the loss of lean muscle mass and bone density when used long-term. Questions also persist around sustained weight loss which require long-term, real-world studies.
In 2022 and 2023, GLP-1 based medications were in short supply, leading individuals to seek alternatives. This has led to the compounding of GLP-1 medications. Shortages have been resolved, leasing the FDA to issue guidance cautioning against compounding when approved products are available. According to the agency, compounding introduces significant concerns, including variability in dosing, accuracy, stability and safety risks.
Although GLP-1s have shown significant benefit in the treatment of obesity, careful attention must be paid to long-term safety and integration into comprehensive care models. It is critical that those who are using the drugs balance the benefits with caution, ensuring they use them in a manger that maximizes benefit, minimizes harm and aligns with the broader goal of public health.
