Benefits and risks of popular weight-loss drugs revealed

Demand for weight loss medications sold under brand names such as Ozempic and Wegovy continues to rise, with a recent survey showing that one in eight Americans have used or are 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, the media, patients, and even some doctors have called GLP-1 drugs “miracle drugs” because of the profound weight loss among users. Although these health benefits are well known, there is little information about the effects of the drugs on the body’s organ systems.

Now scientists from Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health Care System have systematically evaluated the health outcomes of more than 2 million people with diabetes taking the popular weight-loss drugs. They found widespread associations with benefits for cognitive and behavioral health, while also revealing increased risks of pancreatitis and kidney disease, among others.

The study was published on January 20 in the journal Nature Medicine.

“Given the novelty and skyrocketing popularity of the drugs, 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 WashU Medicine-affiliated John J. Cochran Veterans Hospital in St. Louis.

Our approach has allowed us to establish a comprehensive atlas mapping the associations of GLP-1RA across organ systems. The study results provide insight into some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and drive research agendas.”

Ziyad Al-Aly, MD, clinical epidemiologist and nephrologist

The drugs, taken by injection once a week, simulate naturally produced hormones that suppress appetite and slow digestion, creating longer-lasting satiety. A healthy diet and exercise also help with weight loss.

For the study, researchers at WashU Medicine 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 used GLP-1RA medications to treat their diabetes and those who used more traditional medications 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. The patients included people of different ages, races and genders.

GLP-1RA drugs have been associated with significant neurological and behavioral health benefits, with reduced risks of seizures and addiction to substances such as alcohol, cannabis, stimulants and opioids. People taking the weight-loss drugs also experienced a reduced risk of suicidal thoughts, self-harm, bulimia and psychotic disorders such as schizophrenia.

WashU Medicine’s findings also showed a reduced risk of neurocognitive disorders such as Alzheimer’s disease and dementia.

“Interestingly, GLP-1RA drugs act on receptors expressed in brain regions involved in impulse control, reward and addiction – which may explain their effectiveness in curbing appetite and addictive disorders,” says Al-Aly, the director of the Clinical Epidemiology Center at the VA St. Louis Health Care System, where he heads research and development. “These drugs also reduce inflammation in the brain and result in weight loss; both factors may improve brain health and explain the reduced risk of conditions such as Alzheimer’s disease and dementia.”

Although GLP-1RA drugs are effective for a wide range of health conditions, the magnitude of associated benefits is modest: a reduction of about 10 to 20 percent for most outcomes. “However, the modest effect does not detract from the potential value of these drugs, especially for conditions where there are few effective treatment options, for example dementia,” Al-Aly said. “This may also imply that these medications are most helpful when used in combination with other interventions, such as lifestyle changes or other medications.”

The study also confirmed past research findings that described the drugs’ potential to lower the risk of heart attack, stroke and other cardiovascular problems.

Al-Aly stressed that his research also revealed possible drawbacks of the drugs, including an increased risk of gastrointestinal problems such as nausea, vomiting, diarrhea and in rare cases, stomach paralysis. “These are well documented in research and anecdotally,” Al-Aly said. “Our study confirmed such findings.”

But what’s new are the possible ways that GLP-1RA drugs can negatively affect the pancreas and kidneys. Although these side effects are uncommon, they can be very serious; Doctors should be vigilant for signs of pancreatitis and monitor kidney function in people taking GLP-1RA medications. Kidney problems can occur without symptoms until the condition reaches an advanced stage with limited treatment options.

“GLP-1RA drugs may have broad health benefits,” Al-Aly said. “However, they are not without risks. Our findings underline the potential for broader applications for these drugs, but also highlight important risks that should be carefully monitored in people taking these drugs.”