Weight-loss medications are surging in popularity, with a recent study revealing that one in eight Americans has used these drugs to address diabetes, heart disease, or obesity.
A new study, published on Monday (January 20) in Nature Medicine, offers new insights into the effects of these medications, formally known as glucagon-like peptide-1 receptor agonists (GLP-1RA).
This class of drugs, which include Wegovy, Mounjaro and Zepbound, has been dubbed “miracle drugs” by media, patients, and even physicians due to their dramatic impact on weight loss. However, while their health benefits are widely recognized, questions about their impact on the body’s organ systems remain.
Researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health Care System analyzed data from more than two million people with diabetes to address the knowledge gap on the impact of these drugs on body’s organ systems.
Their findings revealed significant benefits to cognitive and behavioral health but also highlighted risks such as pancreatitis and kidney-related complications.
(Image: Photo by: Michael Siluk/UCG/Universal Images Group via Getty Images)
What are GLP-1 receptor agonists and how do they work?
GLP-1 agonists (also called GLP-1 receptor agonists or GLP-1RA) are a class of medications primarily used to manage blood sugar levels in individuals with Type 2 diabetes, with some also helping to treat obesity.
Most GLP-1 agonists are administered via injection, using a needle and syringe to deliver the medication into the fatty tissue just beneath the skin (subcutaneous injection). Common injection sites include the abdomen, outer thighs, upper buttocks, and the backs of the arms.
These medications work in several ways. They:
- stimulate the body to produce more insulin when necessary (insulin helps regulate blood sugar levels)
- reduce the amount of sugar the liver produces
- slow down food digestion so that sugar from meals is absorbed more gradually
- help reduce appetite
“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 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.
“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems,” he said. “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.”
Taken once a week by injection, GLP-1RA drugs mimic naturally occurring hormones that suppress appetite and slow digestion, promoting a sense of prolonged fullness. While weight loss is further supported by a healthy diet and exercise, these medications are showing impacts far beyond the scale.
The researchers from Washington University School of Medicine in St. Louis analyzed medical records from a U.S. Department of Veterans Affairs database to uncover how these drugs affect overall health.
(Image: Getty Images)
Comparing 175 health outcomes, they examined data from veterans who used GLP-1RA drugs for diabetes treatment against those who relied on traditional medications like Jardiance, Glipizide, and Januvia.
The dataset examined over two million veterans treated for diabetes between October 2017 and December 2023, spanning diverse ages, races, and genders.
The findings linked GLP-1RA drugs to significant neurological and behavioral health benefits, including reduced risks of seizures and substance addictions, such as alcohol, cannabis, stimulants, and opioids. Users of the drugs also had lower rates of suicidal ideation, self-harm, bulimia, and psychotic disorders like schizophrenia.
Notably, the study also uncovered a decreased risk of neurocognitive disorders such as Alzheimer’s and dementia, underscoring the broader potential of these medications beyond weight loss.
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“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,” said Al-Aly, the director of the Clinical Epidemiology Center at the VA St. Louis Health Care System, where he is head of the research and development service.
“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 show promise in addressing a range of health issues, the benefits tend to be modest, with most outcomes improving by just 10 to 20 percent.
(Image: Getty Images)
“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 said. “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 reinforced previous findings, showing that GLP-1RA drugs can lower the risk of heart attacks, strokes, and other cardiovascular issues.
However, Al-Aly cautioned that the medications come with potential drawbacks. Among them were an increased risk of gastrointestinal side effects, including nausea, vomiting, and diarrhea. In rare cases, the drugs may even lead to stomach paralysis.
“These have been well documented in the research and anecdotally,” Al-Aly said. “Our study confirmed such findings.”
What sets this study apart is its focus on the potential risks GLP-1RA drugs pose to the pancreas and kidneys. Though these side effects are rare, they can be severe. Physicians are urged to remain vigilant, monitoring for signs of pancreatitis and closely tracking kidney function in patients using these medications.
Kidney issues, in particular, can develop silently, often remaining undetected until the condition is advanced and treatment options become limited.
“GLP-1RA drugs can have broad health benefits,” Al-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 should be carefully monitored in people taking these drugs.”
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