GLP-1 drugs may improve survival of people with brain metastases

medwireNews: People with cancer brain metastases and type 2 diabetes might derive a survival benefit from the use of glucagon-like peptide (GLP)-1 receptor agonists, suggests a database analysis.

The all-cause mortality risk over up to 3 years of follow-up from brain metastasis diagnosis was a significant 37% lower for individuals who did versus did not use GLP-1 receptor agonists, report the study authors in a research letter to JAMA Network Open.

“These results build upon existing evidence that GLP-1 receptor activation modulates pathways relevant to neuro-oncologic health, including attenuation of neuroinflammation, preservation of blood–brain barrier integrity, and reduction of oxidative stress and mitochondrial dysfunction,” they write.

Chien-Min Chen, from Changhua Christian Hospital in Taiwan, and co-investigators collated data for the period between January 2018 and January 2024 from the TriNetX Global Network on 11,969 cancer patients with brain metastases and type 2 diabetes. Of these, 866 were prescribed GLP-1 receptor agonists in the 6 months before the diagnosis of brain metastases and the remaining 11,103 were not.

After propensity score matching, each group comprised 850 individuals, aged an average of 64.5–65.0 years. Just over half (54.2–55.3%) were women and the majority (71.8–73.5%) were White. The most common tumor type was lung cancer (36.0–36.7%), followed by breast cancer (16.5–17.8%), and melanoma (8.4–9.4%).

The researchers found that the mortality benefit of GLP-1 receptor agonists observed in the overall cohort was maintained when analyzing by tumor type, with significant hazard ratios (HRs) for all-cause mortality of 0.75, 0.55, and 0.66 for lung cancer, breast cancer, and melanoma, respectively.

The HRs for all-cause mortality with GLP-1 receptor agonist use varied from a significant 0.38 for semaglutide and 0.75 for dulaglutide, but a nonsignificant 0.96 for liraglutide.

And the mortality benefit also remained consistent when considering use alongside other antidiabetic therapies, such as sulfonylurea and insulin, report Chen and colleagues.

They acknowledge the limitations of the analysis such as the inability to draw causal inferences due to the retrospective nature and “the lack of individual-level data [precluding] dose-response analyses, detailed assessment of concomitant systemic and radiation therapies, and evaluation of cancer-specific mortality.”

Nevertheless, the team believes that “future prospective studies to further elucidate the effects of GLP-1 [receptor agonists] in cancer populations” are warranted.

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JAMA Netw Open 2026; 9: e261311