Benefits and risks of popular weight loss drugs revealed

Benefits and risks of popular weight loss drugs revealed

Demand for weight-loss drugs sold under brand names like Ozempic and Wegurchaden continues to rise, with a recent study reporting 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, media, patients and even some doctors have dubbed GLP-1 drugs "miracle drugs" due to the profound weight loss among users. While these health benefits are well established, information about the drugs' effects in the body's organ systems is sparse.

Now, researchers at Washington University School of Medicine in St. Louis and the St. Louis Health Care System at Veterans Affairs (VA) have systematically assessed health outcomes in more than 2 million people with diabetes who take the popular weight-loss medications. They found widespread associations with cognitive and behavioral health benefits, showing increased risks of pancreatitis and kidney disease, among other things.

The study will be published Jan. 20 in the journal Nature Medicine.

"Given the newness of the drugs and their exploding 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 study senior author Ziyad Al-Aaly, 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 enabled us to build a comprehensive atlas mapping of GLP-1RA associations spanning all organ systems. The results of the study 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-Au-outside, clinical epidemiologist and nephrologist

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

For the study, Washu Medicine researchers analyzed 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 data set examined more than 2 million veterans treated for diabetes from October 1, 2017 to December 31, 2023. Patients included people of different ages, races and genders.

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

Washu Medicine's results also showed a reduced risk of neurocognitive diseases such as Alzheimer's and dementia.

"Interestingly, GLP-1RA drugs act on receptors expressed in brain areas, The VA St. Louis Health Care System, where he is director of research and development services. "These drugs also reduce inflammation in the brain and lead to weight loss. Both factors can improve brain health and explain the reduced risk of diseases such as Alzheimer's disease and dementia."

While GLP-1RA drugs demonstrate effectiveness against a variety of health problems, the magnitude of the associated benefits is small - about 10 to 20 percent reduction in most outcomes. “However, the modest effect does not negate the potential value of these drugs, particularly in conditions where, for example, few effective treatment options exist,” Al-Außer said. “This may also mean that these medications are most beneficial in conjunction with other interventions such as lifestyle changes or other medications.”

The study also confirmed previous research describing the drugs' potential to reduce the risk of heart attack, stroke and other cardiovascular concerns.

Al-Aaly stressed that his study also highlighted potential downsides to the drugs, 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 research and anecdotally,” Al-Außer said. “Our study confirmed such results.”

But what's novel are the potential ways GLP-1RA drugs may negatively affect the pancreas and kidneys. While these adverse effects are uncommon, they can be very serious; Doctors need to be alert for signs of pancreatitis and monitor kidney function in people taking GLP-1RA medications. Kidney problems can occur without symptoms until the disease is in an advanced stage with limited treatment options.

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

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