Summary: Scientists have systematically evaluated the benefits and risks of GLP-1 medications, such as Ozempic and Zepbound, among more than 2 million users. These drugs, widely used for weight loss and diabetes management, were associated with cognitive and behavioral health benefits, including reduced risks of addiction, dementia, and neurocognitive disorders. However, they also pose risks, such as pancreatitis and kidney issues, highlighting the need for careful monitoring by healthcare providers.
Key Takeaways:
- Cognitive and Behavioral Benefits: GLP-1 drugs were linked to reduced risks of addiction, neurocognitive disorders like Alzheimer’s and dementia, and psychiatric conditions such as suicidal ideation and psychosis.
- Potential Serious Risks: While rare, GLP-1 drugs may increase risks for pancreatitis and kidney issues, emphasizing the need for vigilant patient monitoring.
- Broader Implications for Use: The study highlights the potential for expanded applications of GLP-1 medications but underscores that their modest benefits are best realized when combined with other interventions, such as lifestyle changes or additional therapies.
Demand for weight-loss medications sold under brand names such as Ozempic and Zepbound—the first US Food and Drug Administration-approved medication for moderate-to-severe obstructive sleep apnea (OSA) and obesity—continues to surge, with a recent study reporting one in eight Americans has taken or is currently using the drugs to treat diabetes, heart disease, or obesity.
Formally, these drugs are known as glucagon-like peptide-1 receptor agonists (GLP-1RA) and include Mounjaro and Wegovy. Informally, media, patients, and even some physicians have dubbed GLP-1 medications as “miracle drugs” because of the profound weight loss among users. While these health benefits are well established, information is sparse on the drugs’ effects across the body’s organ systems.
Now, scientists at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System have systematically evaluated health outcomes among more than 2 million people with diabetes taking the popular weight-loss drugs. They found widespread associations with benefits to cognitive and behavioral health, while also revealing increased risks for pancreatitis and kidney conditions, among others.
The study is published in the journal Nature Medicine.
Examining the Effects on All Body Systems
“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,” says the study’s senior author, Ziyad Al-Aly, MD, a clinical epidemiologist and nephrologist who treats patients at the WashU Medicine-affiliated John J. Cochran Veterans Hospital in St. Louis, in a release.
He continues, “Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems. The study’s results provide insights into some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research agendas.”
The drugs, 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 assist with weight loss.
For the study, WashU Medicine researchers analyzed de-identified medical records in a database maintained by the US 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 medications sold under brand names such as Jardiance, Glipizide, and Januvia.
Altogether, the dataset examined more than 2 million veterans who were treated for diabetes from Oct 1, 2017, to Dec 31, 2023. Patients included people of diverse ages, races, and sexes.
GLP-1s Linked to Neurological and Behavioral Health Benefits
GLP-1RA drugs were associated with significant benefits to neurological and behavioral health, with reduced risks of seizures and addiction to substances such as alcohol, cannabis, stimulants, and opioids. People taking the weight-loss drugs also experienced decreased risks of suicidal ideation, self-harm, bulimia, and psychotic disorders such as schizophrenia.
WashU Medicine’s findings also showed a decreased risk of neurocognitive disorders such as Alzheimer’s and dementia.
“Interestingly, GLP-1RA drugs act on receptors that are expressed in brain areas involved in impulse control, reward, and addiction—potentially explaining their effectiveness in curbing appetite and addiction disorders,” says Al-Aly, the director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, where he is head of the research and development service, in a release. “These drugs also reduce inflammation in the brain and result in weight loss; both these factors may improve brain health and explain the reduced risk of conditions like Alzheimer’s disease and dementia.”
While GLP-1RA drugs display effectiveness against a wide array of health problems, the magnitude of associated benefits is modest—about a 10 to 20% reduction for most outcomes. “However, the modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” Al-Aly says in a release. “This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”
The study also confirmed past research findings detailing the drugs’ potential to lower the risk of heart attack, stroke, and other cardiovascular concerns.
“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems,” says Al-Aly in a release. “The study’s results provide insights into some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research agendas.”
Potential Downsides to GLP-1s
Al-Aly emphasizes that his study also highlighted potential downsides to the medications, including an increased risk of gastrointestinal problems such as nausea, vomiting, diarrhea, and in rare cases paralysis of the stomach. “These have been well documented in the research and anecdotally,” Al-Aly says. “Our study confirmed such findings.”
But what is novel is the potential ways GLP-1RA drugs can negatively affect the pancreas and kidneys. While these adverse effects are uncommon, they can be very serious; physicians must be vigilant for signs of pancreatitis and monitor kidney function among people taking GLP-1RA medications. Kidney problems can occur without symptoms until the condition is at an advanced stage with limited treatment options.
“GLP-1RA drugs can have broad health benefits,” Al-Aly says in a release. “However, they are not without risks. Our findings underscore the possibility for wider applications for these medications but also highlight important risks that should be carefully monitored in people taking these drugs.”
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