GLP-1 medications are associated with a lower risk of dementia and addiction, but a higher risk of kidney, pancreatic, and gastrointestinal problems.
The demand for weight loss medications, including popular brands like Ozempic and Wegovy, continues to rise. A recent study found that one in eight Americans have used or currently use these medications to manage diabetes, heart disease or obesity.
These drugs, officially classified as glucagon-like peptide-1 receptor agonists (GLP-1RA), include drugs such as Mounjaro and Zepbound. Often referred to as “wonder drugs” by the media, patients and even some doctors, GLP-1 drugs are celebrated for their significant effects on weight loss. Although their benefits are well documented, little is known about the impact of these medications on various organ systems.
In response, researchers from the Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health System conducted an extensive study involving more than 2 million people with diabetes who were taking GLP-1 medications. Their results revealed notable benefits for cognitive and behavioral health, but also identified increased risks of pancreatitis, kidney problems and other health problems.
The study was recently published in the journal Natural medicine.
“Given the newness of these drugs and their growing popularity, it is important to systematically examine their effects on all systems of the body – leaving nothing behind – to understand what they do and what they do not do ” said lead study author Ziyad Al. -Aly, MD, a clinical epidemiologist and nephrologist who treats patients at John J. Cochran Veterans Hospital, affiliated with WashU Medicine, in St. Louis.
“Our approach allowed us to construct a comprehensive atlas mapping GLP-1RA associations spanning all organ systems,” he said. “The study results provide insight into some known and previously unknown benefits and risks of GLP-1RA that may be useful in informing clinical care and guiding research programs.
Mechanisms and benefits of GLP-1RA drugs
The medications, taken once a week by injection, simulate naturally produced hormones that curb appetite and slow digestion, creating longer-lasting satiety. A healthy diet and exercise also contribute to weight loss.
For the study, WashU Medicine researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs. They compared 175 health outcomes between veterans who took GLP-1RA drugs to treat their diabetes and those who took more traditional drugs sold under brand names such as Jardiance, Glipizide and Januvia.
In total, the dataset examined more than 2 million veterans treated for diabetes between October 1, 2017 and December 31, 2023. Patients included people of varying ages, races and genders.
GLP-1RA medications have been associated with significant neurological and behavioral health benefits, with reduced risks of seizures and dependence on substances such as alcohol,
” data-gt-translate-attributes=”({“attribute=”” tabindex=”0″ role=”link”>cannabisstimulants and opioids. People taking weight loss medications also had decreased risks of suicidal ideation, self-harm, bulimia, and psychotic disorders such as schizophrenia.
The WashU Medicine results also showed a decreased risk of neurocognitive disorders such as
” data-gt-translate-attributes=”({“attribute=”” tabindex=”0″ role=”link”>Alzheimer and dementia.
How GLP-1RA drugs impact brain health
“Interestingly, GLP-1RA drugs act on receptors expressed in brain areas involved in impulse control, reward and addiction, which could explain their effectiveness in reducing appetite disorders and addiction,” said Al-Aly, director of the Center for Clinical Epidemiology. at the VA St. Louis Health Care System, where he directs the research and development department. “These medications also reduce inflammation in the brain and cause weight loss; both factors may improve brain health and explain the reduced risk of diseases like Alzheimer’s and dementia.
Although GLP-1RA drugs are effective against a wide range of health conditions, the magnitude of associated benefits is modest: approximately 10 to 20 percent reduction for most outcomes. “However, this modest effect does not negate the potential value of these drugs, especially for conditions for which there are few effective treatment options, for example dementia,” Al-Aly said. “It may also imply that these medications are more beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”
The study also confirmed findings from previous research detailing the drugs’ potential to reduce the risk of heart attacks, strokes and other cardiovascular problems.
Al-Aly pointed out that his study also highlighted potential harms of the drugs, including an increased risk of gastrointestinal problems such as nausea, vomiting, diarrhea and, in rare cases, paralysis of the stomach. ‘stomach. “These have been well documented in research and anecdotally,” Al-Aly said. “Our study confirmed these results.”
But what’s new are the ways GLP-1RA drugs can negatively affect the pancreas and kidneys. Although these side effects are rare, they can be very serious; Physicians should be alert for signs of pancreatitis and monitor kidney function in people taking GLP-1RA medications. Kidney problems may occur without symptoms until the disease is in advanced stages with limited treatment options.
“GLP-1RA drugs may have broad health benefits,” Al-Aly said. “However, they are not without risks. Our results highlight the possibility of broader applications for these drugs, but also highlight important risks that should be carefully monitored in people taking these drugs.
Reference: “Mapping the Efficacy and Risks of GLP-1 Receptor Agonists” by Yan Xie, Taeyoung Choi and Ziyad Al-Aly, January 20, 2025, Natural medicine.
DOI: 10.1038/s41591-024-03412-w
The study was funded by the U.S. Department of Veterans Affairs.
