A look at what the past year of global research has identified about possible associations with this increasingly used drug class.
As more people use glucagon-like peptide-1 receptor agonists for longer, researchers are uncovering effects that extend beyond their established roles in diabetes and weight management.
The past couple of years have seen a transformation in how these drugs are viewed and used in Australia.
Since the Therapeutic Goods Administration approved GLP-1 RAs for chronic weight management towards the end of 2024, there has been an ongoing push to add them to the Pharmaceutical Benefits Scheme for this indication (including PBAC and WHO recommendations), alongside new phase 3 trials of oral formulations, expanded indications, and the rise of unapproved “peptides” being marketed to consumers.
At the same time, global research into the potential benefits and risks of GLP-1 RAs has accelerated and researchers are beginning to identify associations beyond their established effects on blood glucose, weight, and cardiovascular risk.
Several large observational studies published over the past year have highlighted some unexpected signals – both potentially beneficial and potentially harmful.
Lower risk of progression to metastatic cancer
A study from earlier this year raised a potentially significant new question about whether GLP-1 RAs could have anticancer effects, reporting an association between treatment and lower rates of metastatic progression across several solid tumours.
Researchers analysed 10,225 patients with stage I–III cancer who started a GLP-1 RA after their cancer diagnosis.
Patients receiving GLP-1 RAs were propensity-matched with patients taking DPP-4 inhibitors, with matching accounting for factors including demographics, BMI, glycaemic measures, smoking, comorbidities, cancer treatment, screening frequency, and other medications.
The analysis covered seven cancers: breast, prostate, non-small cell lung (NSCLC), colorectal, hepatocellular, renal cell, and pancreatic cancer.
GLP-1 RA use was associated with a lower risk of progression to stage IV disease in six of the seven cancers studied, although the reduction only reached statistical significance in four.
The strongest association was seen in NSCLC, where the cumulative incidence of progression was 10.0% among GLP-1 RA users compared with 22.3% among DPP-4 inhibitor users (HR 0.50; 95% CI, 0.43–0.59; P<0.001).
Significant reductions were also reported for breast cancer (10.2% vs 20.1%; HR 0.57; 95% CI, 0.46–0.71; P<0.001), hepatocellular carcinoma (18.9% vs 28.4%; HR 0.62; 95% CI, 0.44–0.89; P=0.009), and colorectal cancer (13.4% vs 22.2%; HR 0.69; 95% CI, 0.54–0.88; P=0.003).
The associations were not statistically significant for prostate cancer (HR 0.79; 95% CI, 0.60–1.04), renal cell carcinoma (HR 0.95; 95% CI, 0.71–1.29), or pancreatic cancer (HR 0.69; 95% CI, 0.42–1.13).
Additionally, the researchers looked at GLP-1 receptor expression within tumours across the cohort. Higher expression was associated with better overall survival across all seven cancer types (HR 0.67; 95% CI, 0.54–0.83; P<0.001), with the strongest association observed in breast cancer (HR 0.55; 95% CI, 0.35–0.87; P=0.011).
“GLP-1RA initiation after cancer diagnosis was associated with dramatically reduced metastatic progression across multiple solid tumours,” the authors concluded.
“Corroborating these clinical findings, elevated GLP-1R expression independently predicted improved overall survival.”
No significant safety signals or increase in adverse events were identified among GLP-1 RA users compared with controls.
Journal of Clinical Oncology, 27 May 2026
Lower subarachnoid haemorrhage risk
Another study identified a potentially protective association between GLP-1 RA use and non-traumatic subarachnoid haemorrhage (SAH) among people with intracranial aneurysms and type 2 diabetes.
Researchers conducted a retrospective cohort study using a database of more than 90 healthcare organisations across North and South America, Europe, and Asia, with most data coming from the US.
The study included patients with unruptured intracranial aneurysms and type 2 diabetes between 2010 and 2025 who were either receiving a GLP-1 RA (n = 2517) or another glucose-lowering medication (n = 23,431). After propensity score matching across 95 demographic and clinical characteristics (including smoking and hypertension), 2275 patients remained in each group.
Over a maximum five-year follow-up period, GLP-1 RA use was associated with a lower risk of non-traumatic SAH (HR 0.66; 95% CI, 0.50–0.87) and all-cause mortality (HR 0.63; 95% CI, 0.52–0.76).
Subgroup analysis, which excluded patients who had previously undergone treatment for their aneurysm, found similar results: GLP-1 RA use was associated with lower risks of SAH (HR 0.68; 95% CI, 0.47–0.98) and all-cause mortality (HR 0.64; 95% CI, 0.53–0.77).
The researchers also examined a broader group of patients without diabetes. After adjustment, GLP-1 RA use remained associated with a lower incidence of non-traumatic SAH (HR 0.62; 95% CI, 0.50–0.76).
Among patients who did develop non-traumatic SAH, GLP-1 RA use was associated with lower all-cause mortality (HR 0.36; 95% CI, 0.26–0.51), hydrocephalus (HR 0.49; 95% CI, 0.31–0.77), and cognitive decline (HR 0.74; 95% CI, 0.56–0.97). No significant associations were seen with shunt dependency, caregiver dependency, or headache.
The researchers suggested that the anti-inflammatory and blood pressure-lowering effects of GLP-1 RAs could potentially contribute to the observed association.
Possible bone benefits
A study of deidentified electronic health records from 151 healthcare organisations worldwide found an association between GLP-1 RA use and a lower risk of vertebral compression fractures.
Adults with type 2 diabetes diagnosed between 2015 and 2022 were included – 259,162 GLP-1 RA users and 1,289,637 non-users.
The analysis focused on semaglutide, liraglutide and dulaglutide, which were the most commonly used GLP-1 RAs in the dataset. People with previous vertebral fractures, inflammatory spondylopathies, vertebral malignancy, or previous vertebroplasty or kyphoplasty were excluded.
GLP-1 RA use was associated with lower odds of vertebral compression fracture, occurring in 1.5% of users compared with 1.8% of non-users (OR 0.83; 95% CI, 0.79–0.87). The need for surgical intervention such as vertebroplasty or kyphoplasty was also lower among GLP-1 RA users (0.08% vs 0.10%; OR 0.80; 95% CI, 0.65–0.99).
“The mechanisms underlying this association are likely multifactorial,” authors wrote.
“GLP-1 RAs may directly promote bone formation and inhibit resorption by modulating osteoblast and osteoclast activity through the RANKL/OPG signalling pathway. They may also enhance bone microarchitecture by affecting calcium and phosphate metabolism and regulation of bone-related hormones through the hypothalamic-pituitary-parathyroid axis.
“Furthermore, GLP-1 RAs mitigate chronic inflammation and insulin resistance, which may preserve osteoblast function and bone matrix quality, thereby reducing skeletal fragility.”
They also noted that due to the observational design and the inconsistent findings in previous research of fracture risk, the possible bone-protective association cannot yet be established.
Erectile dysfunction signal
Another observational analysis raised a possible association between GLP-1 RA use and erectile dysfunction (ED) in men with type 2 diabetes, although further analysis weakened the signal.
Researchers conducted a target trial emulation using electronic health records from a US health system between 2019 and 2024. The study included adult men with type 2 diabetes who had initiated either a GLP-1 RA (n = 4910) or a DPP-4 inhibitor (n = 5524) with new diagnoses of ED being the primary outcome.
ED occurred at a rate of 35.2 cases per 1000 person-years among GLP-1 RA users compared with 28.0 per 1000 person-years among DPP-4 inhibitor users (HR 1.26; 95% CI, 1.08–1.46).
The difference was substantially larger before adjustment, when the incidence rates were 44.4 vs 24.6 cases per 1000 person-years and the HR was 1.78 (95% CI, 1.57–2.02), suggesting that differences between the treatment groups accounted for a considerable proportion of the initial association.
Results were generally consistent across subgroup and sensitivity analyses and were also observed in an external international validation cohort.
However, the association was attenuated and was no longer statistically significant after calibration using a negative-control outcome, adding to uncertainty about whether the association was causal.
The Lancet eClinical Medicine, 2 April 2026
Increased chronic cough
A large cohort study identified a possible association between GLP-1 RA use and newly diagnosed chronic cough, independent of a previous diagnosis of gastroesophageal reflux disease (GORD).
The study used electronic medical records from 70 US healthcare organisations covering 2005 to 2025. It included 427,555 adults with type 2 diabetes who had been prescribed a GLP-1 RA and 1,614,495 patients prescribed another second-line diabetes medication, including DPP-4 inhibitors, SGLT2 inhibitors, or sulfonylureas.
After propensity score matching, GLP-1 RA use was associated with a higher risk of newly diagnosed chronic cough than any non-GLP-1 RA second-line medication (adjusted hazard ratio [aHR] 1.12; 95% CI, 1.08–1.16). The association was also observed when GLP-1 RAs were compared specifically with DPP-4 inhibitors (aHR 1.18; 95% CI, 1.11–1.26) and sulfonylureas (aHR 1.32; 95% CI, 1.24–1.40), but not SGLT2 inhibitors (aHR 1.03; 95% CI, 0.98–1.09).
The researchers then excluded people with a previous diagnosis of GORD to investigate whether reflux could explain the finding but the association persisted, with GLP-1 RA users having a higher risk of chronic cough compared with patients receiving any non-GLP-1 RA medication (aHR 1.29; 95% CI, 1.17–1.42), DPP-4 inhibitors (aHR 1.36; 95% CI, 1.17–1.58), SGLT2 inhibitors (aHR 1.14; 95% CI, 1.02–1.28) and sulfonylureas (aHR 1.25; 95% CI, 1.09–1.42).
The authors noted that although GLP-1 RAs have been linked with GORD and can affect vagal nerve signalling, an association with chronic cough had not previously been investigated.
JAMA Otolaryngology – Head & Neck Surgery, 29 September 2025
All of these studies share similar strengths and weaknesses; large, long-term cohorts to identify possible associations and propensity matching to strengthen analyses, but observational design can’t establish causation.
Regulatory scrutiny continues
These emerging associations come as regulators continue to monitor the safety profile of GLP-1 RAs as their use expands.
We’ve recently seen new alerts from the TGA warning of a potential increase in suicidality and vision disorder associated with some GLP-1 RAs, and the UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently updated its warnings to include necrotising and fatal pancreatitis – an association currently being investigated for a possible genetic link.
