Are popular weight loss drugs putting your patients at risk?

Are weight-loss drugs dangerous to patients? ©Tobias Arhelger - stock.adobe.com

The popularity of weight-loss medications such as Ozempic and Wegovy continues to soar, with a new study reporting that one in eight Americans has used these drugs to address diabetes, heart disease, or obesity. Known as glucagon-like peptide-1 receptor agonists (GLP-1RA), these drugs also include Mounjaro and Zepbound, earning the informal label of “miracle drugs” due to their profound effects on weight loss and related health outcomes. However, research from Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System examined both the extensive benefits and potential risks of the drugs.

In a study published January 20 in Nature Medicine, scientists evaluated the health outcomes of over two million people with diabetes who were prescribed GLP-1RA medications. The findings highlight the drugs' broad effects on neurological and behavioral health, alongside increased risks for specific conditions such as pancreatitis and kidney issues.

“Given the drugs’ newness and skyrocketing popularity, it is important to systematically examine their effects on all body systems — leaving no stone unturned — to understand what they do and what they don’t do,” said senior author Ziyad Al-Aly, M.D., a clinical epidemiologist and nephrologist at Washington University. “Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems.”

Using de-identified medical records from the U.S. Department of Veterans Affairs, the researchers compared 175 health outcomes in veterans taking GLP-1RA drugs versus those prescribed traditional diabetes medications such as Jardiance, Glipizide, and Januvia. The analysis included patients of diverse ages, races, and sexes, providing robust data to inform clinical care.

Among the study's key findings, GLP-1RA drugs were associated with significant benefits to neurological and behavioral health. Patients experienced reduced risks of conditions such as seizures, addiction disorders (including alcohol, cannabis, stimulants, and opioids), suicidal ideation, and psychotic disorders like schizophrenia. The drugs were also linked to lower risks of neurocognitive conditions such as Alzheimer’s disease and dementia.

“Interestingly, GLP-1RA drugs act on receptors expressed in brain areas involved in impulse control, reward, and addiction — potentially explaining their effectiveness in curbing appetite and addiction disorders,” said Al-Aly. “These drugs also reduce inflammation in the brain and result in weight loss; both these factors may improve brain health.”

Echoing previous studies, the research confirmed GLP-1RA drugs’ ability to reduce risks of heart attack, stroke, and other cardiovascular concerns. The magnitude of benefits was modest, generally ranging from a 10% to 20% reduction. Still, Al-Aly emphasized the potential value of these drugs, particularly for conditions with limited treatment options. “The modest effect does not negate the potential value of these drugs, especially for conditions like dementia,” he said. “They are likely most effective when used alongside lifestyle changes or other medications.”

Risks: Pancreatitis, kidney problems, and GI issues

While GLP-1RA drugs show promise, the study also underscored risks, including gastrointestinal issues such as nausea, vomiting, and diarrhea. More notably, researchers identified associations with rare but serious complications involving the pancreas and kidneys.

“Our findings highlight important risks that should be carefully monitored in people taking these drugs,” Al-Aly said. “Physicians must remain vigilant for signs of pancreatitis and routinely monitor kidney function, as kidney problems often progress silently until they are at an advanced stage.”

As the use of GLP-1RA medications grows, this study provides a resource for health care providers navigating the balance between the drugs’ benefits and risks.

“GLP-1RA drugs can have broad health benefits,” Aly-Aly said. “However, they are not without risks. Our findings underscore the possibility for wider applications for these medications but also highlight important risks that must be managed in clinical practice.”