Demand for weight-loss medications sold under brand names such as Ozempic and Wegovy 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 Zepbound. 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 (VA) 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 Jan. 20 in the journal Nature Medicine.

“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. 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.”

Ziyad Al-Aly, MD, clinical epidemiologist and nephrologist 

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 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 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-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,” 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 display effectiveness against a wide array of health problems, the magnitude of associated benefits is modest – about a 10 percent to 20 percent 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 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 confirmed past research findings detailing the drugs’ potential to lower the risk of heart attack, stroke and other cardiovascular concerns.

Al-Aly emphasized 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 said. “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 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.”