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Examining the pros and cons of semaglutide

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The risks and benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide have been compared in a comprehensive evaluation using data from 2.4 million participants.
 
While medications like GLP-1RAs are well-known as effective treatment for management of type 2 diabetes and obesity, the new research suggests they may also lower risks for conditions such as dementia, mental health issues, heart disease and lung issues.
 
Using United States Department of Veterans Affairs databases, an analysis of 175 health outcomes in 215,970 individuals using GLP1-RAs as usual care for type 2 diabetes was compared to individual cohorts who used other common diabetes treatments, such as sulphonylureas, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors.
 
The findings suggest GLP-1RAs are linked with a range of both positive and negative health effects, including a decreased risk of 42 health outcomes and increased risk of 19.
 
Compared to usual care, participants who used GLP-1RAs had a lower risk of:

• substance use and psychotic disorders
• seizures
• neurocognitive disorders including Alzheimer’s disease and dementia
• infectious illnesses
• several respiratory conditions
• coagulation and cardiometabolic disorders, including deep vein thrombosis, pulmonary embolism, stroke, cardiac arrest, heart failure and myocardial infarction.

Conversely, it found patients were at an increased risk of:
 

• gastrointestinal conditions such as nausea and vomiting, diverticulitis, gastritis and abdominal pain
• hypotension
• syncope
• arthritis.

These findings come despite other recent studies showing an increased risk of suicidal ideation among people with anxiety or depression who take semaglutide, compared to other diabetes drugs.
 
In response to the US study, Australian experts have weighed up the pros and cons of GLP-1RA use.

Sydney-based obesity and bariatric medical practitioner Dr Georgia Rigas said the US study represents a ‘fascinating step forward’, providing real-world insights into the ‘far-reaching potential’ of GLP-1RAs.
 
‘This study shows the effects of GLP-1RA medications go beyond just managing blood sugar and weight,’ she said.
 
‘They may also benefit other parts of the body, like reducing the risks of heart disease, lung problems, and even conditions like dementia. It’s like getting bonus health benefits from a single treatment.
 
‘GLP-1 medications not only help with weight loss and blood sugar control but also have a well-studied safety profile.
 
‘This large study found that their side effects are consistent with what we already know, giving us even more confidence in their use.’

In Australia, semaglutide sold as Ozempic has rapidly grown in use since it gained social media popularity as a weight-loss drug, with off-label prescribing prompting ongoing shortages now expected until December 2025.
 
Replica versions began to emerge but have since been banned amid safety concerns, and availability of new drugs targeted for weight loss, Wegovy and Mounjaro, has been expanded.
 
Epidemiologist and public health specialist from the University of Melbourne’s School of Population and Global Health, Professor Tony Blakely, says the US study adds to the ‘growing knowledge of the wide-ranging effects’ of GLP-1RAs.
 
‘[We] will likely see profound changes going forward in treatment of cardiometabolic disorders and diabetes in the future – and the treatment and prevention of obesity, noting this study was among diabetics only,’ he said.

‘For non-diabetics taking GLP agonists for other reasons – most likely reducing body weight – the results of this study may not be applicable as the interaction of diabetes-related inflammation, and such may be the reason for such wide-ranging GLP agonist effects.’

The study authors conclude that their results provide insights into the benefits and risks of GLP-1R and ‘may be useful for informing clinical care and guiding research agendas’.
 
However, they state further research should be explored to include a more diverse cohort of participants, given those from the US Department of Veterans Affairs are mostly older, white males.
 
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GLP-1RA glucagon-like peptide-1 receptor agonists overweight and obesity Ozempic semaglutide type 2 diabetes

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