GLP-1 Agonists Linked to Lower Mortality in Cancer Patients With Brain Metastases: JAMA
USA: A new study has shown that among cancer patients with brain metastases and type 2 diabetes, use of GLP-1 receptor agonists was associated with a 37% lower risk of death over three years. The mortality benefit was significant with semaglutide and dulaglutide, but not with liraglutide. Reduced all-cause mortality was consistently observed among patients with major cancers such as lung and breast cancer.
The findings were published in JAMA Network Open by Kuan-Yu Chi from the Department of Internal Medicine at Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, and colleagues.
Brain metastases are a serious complication of cancer and are linked to high morbidity and mortality. The presence of type 2 diabetes may further worsen outcomes through metabolic and inflammatory mechanisms. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used for diabetes management, have recently attracted attention for their potential neuroprotective and anti-inflammatory properties. However, clinical evidence on their association with outcomes in patients with brain metastases remains limited.
To explore this association, the researchers conducted a retrospective cohort study using the TriNetX Global Network, a large database covering 151 healthcare organizations worldwide. The study included adults diagnosed with cancer, brain metastases, and type 2 diabetes between January 2018 and January 2024.
Patients who received GLP-1 receptor agonists within six months before the first documented diagnosis of type 2 diabetes and brain metastases formed the exposure group, while those with no GLP-1 RA use during the same period served as controls. One-to-one propensity score matching was applied to balance baseline characteristics between the two groups.
Among 19,234 eligible patients, 866 were GLP-1 RA users, and 11,103 were nonusers. After matching, 850 patients in the GLP-1 RA group were compared with 850 nonusers. The GLP-1 RA group included patients treated with semaglutide, dulaglutide, liraglutide, and tirzepatide.
The analysis revealed the following findings:
- Use of GLP-1 receptor agonists was associated with significantly lower all-cause mortality.
- The hazard ratio for death was 0.63.
- This corresponded to a 37% reduction in the risk of death over three years compared with nonusers.
- The survival benefit was consistent across major cancer types.
- The benefit was observed with most GLP-1 receptor agonists, except liraglutide.
- Similar findings were seen when GLP-1 receptor agonists were compared with other antidiabetic therapies.
The researchers also evaluated seizure events and pneumonia as falsification endpoints to assess potential bias from unmeasured confounding factors. The incidence of these events was comparable between the groups, supporting the robustness of the findings.
The authors noted several limitations, including the retrospective design, lack of detailed data on treatment regimens, and limited generalizability because most participating centers were academic institutions. Nonetheless, the findings suggest that GLP-1 receptor agonists may be associated with improved survival in patients with cancer, brain metastases, and type 2 diabetes, highlighting the need for prospective studies to further evaluate their role in oncology populations.
Reference:
Chi K, Chang Y, Song J, Chen C, Perng P, Lin H. GLP-1 Receptor Agonist Use and Survival Among Patients With Type 2 Diabetes and Brain Metastases. JAMA Netw Open. 2026;9(3):e261311. doi:10.1001/jamanetworkopen.2026.1311
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