Ozempic, Wegovy, Zepbound and other drugs often used for weight loss may help lower the risk of a wide range of health conditions, from diabetes to Alzheimer’s, according to a new study, but they also may come with risks like pancreatitis and stomach paralysis.
The large observational study, published Monday in Nature Medicine, is the first of its kind to map the risks and benefits of drugs like Ozempic across 175 potential health outcomes, according to the authors.
These health outcomes ranged from psychotic disorders, seizures and dementia to gastrointestinal disorders, hypotension and arthritis.
“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, a clinical epidemiologist and nephrologist at WashU Medicine in St. Louis, Mo.
“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,” he said in a Monday media release.
Glucagon-like peptide-1 receptor agonists (also known as GLP-1s), including medications like Ozempic, Mounjaro and Zepbound, have gained popularity over the years.
Initially developed to treat Type 2 diabetes, these drugs have become increasingly popular over the past decade for managing diabetes, obesity and other health conditions.
“At a very high level, when you give the drug to somebody, you’re sort of telling the body that it’s just eaten a meal. So the effects that this drug has is that it works on the brain to reduce appetite and to change the craving for food and even other things as this paper shows,” explained Hertzel Gerstein, an endocrinologist and a professor of medicine at McMaster University in Hamilton.
Between 900,000 and 1.4 million Canadians use a GLP-1 drug like Ozempic to manage weight loss and Type 2 diabetes, according to a March 2024 survey by Dalhousie University’s Agri-Food Analytics Lab.
As the popularity of these drugs has grown and more people have started using them, reports of potential risks have also increased, with the most concerning being stomach paralysis and other gastrointestinal issues.
But with this new study, researchers have compiled what they say is the clearest ever picture of the effectiveness and risks associated with taking GLP-1s.
To do this, the researchers looked at the health of 215,000 people with Type 2 diabetes between 2017 and 2023 maintained by the U.S. Department of Veterans Affairs. Patients included people of diverse ages, races and sexes.
They then compared these findings to a control group of over one million individuals using other anti-diabetic drugs. They found that GLP-1 users had a lower risk for 42 different health conditions or adverse events but were at a higher risk for 19 others.
The study found that GLP-1 drugs offered significant benefits for neurological and behavioural health, including lower risks of seizures and substance addiction to things like alcohol, cannabis, stimulants and opioids.
People taking these medications also had reduced risks of suicidal thoughts, self-harm, bulimia and even psychotic disorders like schizophrenia, the study said.
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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,” Al-Aly said in the media release.
“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,” he added.
The findings also revealed a reduced risk of neurocognitive disorders, including Alzheimer’s and dementia — a trend that aligns with emerging evidence from previous research.
An October 2024 study in the journal Alzheimer’s & Dementia found that semaglutide, the active ingredient in Ozempic and Wegovy, appeared to reduce the risk of Alzheimer’s disease in people with Type 2 diabetes.
The study in Nature Medicine also found the medication had the potential to lower the risk of heart attack, stroke and other cardiovascular concerns.
While GLP-1 drugs display effectiveness against a wide array of health problems, the magnitude of associated benefits is modest — about a 10 per cent to 20 per cent reduction for most outcomes, the study found.
“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.”
Side effects are a possibility with any medication, Gerstein explained.
The study confirmed that GLP-1 drugs come with side effects that increase the risks of constipation, diarrhea, stomach upset, mild nausea and occasional vomiting, he said.
The researchers added that many of the risks associated with drugs like Ozempic, including stomach paralysis, have been observed both in research and anecdotally, and their study confirms these findings.
For example, a 2023 study published in JAMA found that these weight loss drugs are associated with an increased risk of stomach paralysis, pancreatitis and bowel obstruction.
The study also found that the drugs increased people’s odds of developing gastrointestinal issues, low blood pressure and arthritis.
However, the study also highlighted additional risks that have not been researched before, including the potential negative effects of GLP-1 drugs on the pancreas and kidneys.
“The study raised the possibility that it might increase the risk of kidney stones, which I have not seen published before, so that’s what’s summarized in this study,” Gerstein said.
“But nothing in medicine works for everybody and nothing has zero side effects. Everything has side effects,” he added.
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, the researchers noted.
“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.”
GLP-1 drugs are backed by large randomized trials that show, “unequivocally,” their ability to do much more than just promote weight loss and lower blood sugar, Gerstein said.
These drugs have been proven to reduce the risk of heart attacks, strokes, heart failure, kidney disease, kidney failure, hospitalizations and even deaths, he said.
“This class of drugs, the GLP-1 receptor agonist class is a huge game changer drug in the management of diabetes,” he said.
However, when looking at these studies he said it’s important to note that these are results for the average person, so what may work for one person may not work for another.
“This does not mean that everybody in the world should go out and get this drug. It means, though, that people should discuss with their physician the options for them and what the benefits and the potential harms and adverse effects are for this drug,” Gerstein said.
He believes the overall benefits of these drugs outweigh the risks for those who need them, but added, “There can be harms, and you cannot dismiss that possibility.”
“You need to have the discussion [with your doctor] as this is not going to be for everybody.”
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