Benefits and risks of popular weight loss drugs revealed

Demand for weight-loss drugs sold under brand names such as Ozempic and Wegovy continues to grow, with a recent study reporting that one in eight Americans have taken 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. Unofficially, the media, patients and even some doctors have called GLP-1 drugs “miracle drugs” because of the profound weight loss among users. While these health benefits are well documented, information is scarce on the effects of drugs on the body’s organ systems.

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

The study is published Jan. 20 in the journal Nature Medicine.

“Given the novelty and increasing popularity of drugs, it’s important to systematically look at their effects across all body systems – no matter what – to understand what they do and don’t do,” said the study’s senior author, Ziyad Al . -Aly, MD, a clinical epidemiologist and nephrologist who treats patients at John J. Cochran Veterans Affairs Affiliated WashU Medicine Hospital in St. Louis.

Our approach allowed us to create a comprehensive atlas mapping GLP-1RA correlates spanning all organ systems. The study results provide information on some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research programs.”

Ziyad Al-Aly, MD, clinical epidemiologist and nephrologist

The drugs, taken once a week by injection, mimic naturally produced hormones that curb appetite and slow digestion, creating satiety that lasts longer. Eating healthy and exercising also help 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 drugs sold under brand names such as Jardiance, Glipizide and Januvia.

Overall, the dataset looked at more than 2 million veterans who were treated for diabetes from October 1, 2017, to December 31, 2023. 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 showed reduced risks of suicidal ideation, self-harm, bulimia nervosa, and psychotic disorders such as schizophrenia.

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

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

While GLP-1RA drugs show efficacy against a wide range of health problems, the magnitude of the 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 there are few effective treatment options, for example, dementia,” Al-Aly said. “This may also mean that these drugs are more beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

The study also confirmed findings from previous research detailing the drugs’ potential to reduce the risk of heart attack, stroke and other cardiovascular problems.

Al-Aly stressed that his study also highlighted potential downsides 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 is new is the potential ways in which GLP-1RA drugs can adversely affect the pancreas and kidneys. Although these side effects are uncommon, they can be very serious. Physicians should be alert for signs of pancreatitis and monitor renal function among people taking GLP-1RA drugs. Kidney problems can occur without symptoms until the condition is at an advanced stage with limited treatment options.

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