Imma Perfetto
Cosmos science journalist
A large analysis of weight-loss drugs like Ozempic and Wegovy has surprised health researchers, who found links to multiple new benefits – and some new side effects.
The research has found that weight-loss drugs – known as glucagon-like peptide 1 receptor agonists (GLP-1RAs) – may be associated with increased risks for pancreatitis and kidney conditions.
The medications, often known by the brand names Ozempic, Wegovy, and Mounjaro, among others, are increasingly being used to treat diabetes and obesity worldwide.
The study looked at the associations between GLP-1RA use and 175 health outcomes in diabetics and compared this to control participants who used other drugs to reduce their blood sugar levels. In total, data from the health records of 2.4 million people was analysed.
The findings are observational and cannot prove cause and effect. But given the drugs’ skyrocketing popularity, Ziyad Al-Aly, a clinical epidemiologist and nephrologist at John J. Cochran Veterans Hospital in the US, says 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,” he says.
Al-Aly is corresponding author of a new Nature Medicine study, which evaluated the health outcomes of almost 216,000 diabetic individuals taking GLP-1RAs and found widespread associations with benefits to cognitive and behavioural health.
“GLP-1RA drugs can have broad health benefits,” Al-Aly says. “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-1RAs mimic the hormone GLP-1, which is naturally produced in the gut. They stimulate insulin production to lower blood sugar levels, and slow digestion and curb appetite.
“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems,” says Al-Aly.
“The study’s results provide insights into some known and previously unrecognised benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research agendas.”
The study found users of GLP-1RAs had 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 says. “Our study confirmed such findings.”
The potential ways GLP-1RA drugs may negatively affect the pancreas and kidneys, however, were new.
Participants who used GLP-1RAs had a lower risk of substance use and psychotic disorders, seizures, neurocognitive disorders – including Alzheimer’s disease and dementia – coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions.
“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,” says Al-Aly.
“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.”
Professor Tony Blakely, an epidemiologist and public health medicine specialist at the University of Melbourne in Australia, who was not involved in the study, says that the results of the study may not be applicable for non-diabetics taking GLP-1RAs for other reasons, such as reducing body weight.
“The interaction of diabetes-related inflammation and such like may be the reason for such wide-ranging GLP agonist effects,” says Blakely.
The researchers acknowledge the use of data on US veterans – who are older, mostly white males and may not represent the general population – as a limitation of the study.
“The new risks and benefits observed are all from observation and need to be confirmed in targeted studies or additional analysis of completed interventions,” adds Peter Clifton, an adjunct research professor of nutrition at the University of South Australia, who was not involved in the research.
“Some of the observations may be explained by the kind of patients given GLP1 agonists and others by the effects of the drugs themselves. For instance, the reduced risks of infections and pulmonary disease and thrombo-embolic disease may be mostly due to the weight loss induced by the GLP1 agonists, while the increased risks of [kidney stones] may due to reduced fluid intake because of nausea and anorexia.
“Other associations such as reduced schizophrenia risk may relate to patient selection. Further research is needed to confirm the results in other cohorts and clinical trials.”
