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14 FEBRUARY 2025 ausdoc . com . au
Eye-opener or just big data ?
GLP-1 RAs linked to reduced risk for dozens of conditions .
Mohana Basu A MAJOR observational study of nearly two million patients with type 2 diabetes has highlighted the potential wideranging health benefits of GLP-1 receptor agonists — but also the potential risks .
Researchers mapped links between the medications and 175 health outcomes , comparing them with those of patients taking other common antiglycaemics — such as sulfonylureas , DPP-4 inhibitors or SGLT2 inhibitors — and those continuing with their usual care .
GLP-1 receptor agonists ( RAs ) were linked to a lower risk for dozens of conditions , including heart disease , stroke and kidney disease .
However , the authors said they had identified new potential beneficial effects beyond those currently recognised , including reduced risk of seizures , bacterial infections and pneumonia .
The drugs were also linked with a lower risk of psychotic disorders by 18 %, Alzheimer ’ s disease by 12 % and opioid use disorders by an average of 13 %.
The research , published in Nature Medicine , also suggested that the drugs may reduce the risk of suicidal ideation and intentional self-harm .
Professor David Henry .
“ It was definitely eye-opening for me to see all these different hits in different organ systems ,” said lead author Dr Ziyad Al-Aly , a clinical epidemiologist at the Washington University School of Medicine in St Louis , Missouri , US .
Some of the benefits of the drugs could be a result of the fact that receptors were found throughout the body , including in the heart and some parts of the immune system , he added .
On the links to reduced risk of substance misuse , he said : “ It is very clear this class of [ drug seems ] to suppress reward mechanisms
‘ The authors caution against basing treatment on these data .’
[ in the brain so they inhibit ] that urge to seek out alcohol , to seek out tobacco , to seek out gambling .”
One major study limitation was using US veterans who were older , mostly white males . Only 5 % of the participants in the study were women .
Among the main side effects identified were increased risks of nausea and vomiting ( 30 %), diverticulitis ( 8 %), gastritis ( 10 %) and abdominal pain ( 12 %).
There was also an increased risk of hypotension ( 6 %), arthritis ( 11 %) and nephrolithiasis ( 15 %) compared with patients not taking GLP-1 RAs .
And researchers also identified a more than twofold higher risk of drug-induced pancreatitis , a new finding on the possible risks of the medications .
Dr Georgia Rigas , former chair of the RACGP Specific Interests Obesity Management group , said the study offered real-world insights into the “ far-reaching potential ” of GLP-1 RAs .
“ It is like getting bonus health benefits from a single treatment .”
Professor David Henry , honorary adjunct professor at the Institute for Evidence-Based Healthcare at Queensland ’ s Bond University , stressed that the study was observational and not a randomised trial .
“ The authors caution against basing treatment recommendations on these data without further confirmation ,” he said . “ Such reticence is justified .
“ Flawed observational studies of another diabetes drug , metformin , concluded erroneously that the drug prevented cancer . Analysis of data from randomised trials disproved that theory .
“ This type of ‘ big data ’ research will generate lots of statistical associations , some of which will be spurious .
“ It is not yet clear whether these datadriven methods for exploring beneficial and harmful drug effects are a genuine advance over traditional inferential approaches .”
Nat Med 2025 ; 20 Jan .
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