GLP-1 Drugs May Benefit Cancer Patients With Brain Lesions

GLP-1 receptor agonist use was associated with a lower risk of death in cancer patients with brain metastases and type 2 diabetes, a retrospective cohort study found.

Within 3 years of a first recorded brain metastasis, patients on a GLP-1 drug had a 37% lower risk of all-cause mortality compared with nonusers (HR 0.63, 95% CI 0.54-0.72), Chien-Min Chen, MD, PhD, of Changhua Christian Hospital in Taiwan, and colleagues reported.

Their matched analysis of 1,700 patients, published in JAMA Network Open, showed the association to be consistent across three of the most common cancer types: lung cancer (HR 0.75, 95% CI 0.62-0.92), breast cancer (HR 0.55, 95% CI 0.38-0.80), and melanoma (HR 0.66, 95% CI 0.44-0.97).

“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,” the research team wrote.

Across the GLP-1 agents examined in a class analysis, the findings were significant for semaglutide (Ozempic, Rybelsus) and dulaglutide (Trulicity), but no apparent benefit was observed with liraglutide (Victoza):

• Semaglutide: HR 0.38 (95% CI 0.29-0.49)
• Dulaglutide: HR 0.75 (95% CI 0.61-0.93)
• Liraglutide: HR 0.96 (95% CI 0.71-1.31)

The findings are interesting, Daniel Drucker, MD, of the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, told MedPage Today, but more patient-level data are needed to determine what drove the association between GLP-1 drug use and lower all-cause mortality.

“A major limitation is we don’t actually know causes of death,” said Drucker, who wasn’t involved with the study. “Was there any evidence for radiological stability of the brain metastases or reduced rates of infection or sepsis? Fewer strokes or myocardial infarctions? These questions need to be separately evaluated in future studies.”

Metastases to the brain in cancer patients are linked with substantial morbidity and mortality, and comorbid type 2 diabetes likely worsens outcomes through metabolic and inflammatory pathways, the researchers explained. GLP-1 agents “have transformed beyond antiglycemic control, with emerging preclinical evidence suggesting potential neuroprotective and anti-inflammatory effects,” they noted.

While prior research on the class of drug’s effects on brain metastases is limited, this wasn’t the first study to show potential benefits of GLP-1 drug use in cancer patients. A 2025 retrospective study found GLP-1 agonist users had a lower risk for 12 of 13 obesity-related cancers, plus lung cancer. Another study published last year reported a 62% lower risk of 5-year mortality in patients with obesity and colon cancer taking GLP-1 drugs.

Chen and co-authors used the TriNetX Global Network, which included data from 151 global healthcare organizations. They identified cancer patients with brain metastases and concurrent type 2 diabetes from January 2018 to January 2024.

After propensity-score matching, 850 GLP-1 drug users were matched to the same number of nonusers. Adults with potential contraindications to GLP-1 agents and those with a lower socioeconomic status were excluded.

The average age was 65 years, 55% were female, and 73% were white. Dulaglutide was the most common GLP-1 drug prescribed, followed by semaglutide and liraglutide. Tirzepatide (Mounjaro) was omitted from the subgroup analysis due to an insufficient number of users.

GLP-1 drugs showed a lower risk for all-cause mortality compared with all other classes of antidiabetic agents examined:

• DPP-4 inhibitors: HR 0.62 (95% CI 0.52-0.74)
• SGLT2 inhibitors: HR 0.68 (95% CI 0.52-0.90)
• Sulfonylureas: HR 0.62 (95% CI 0.52-0.73)
• Thiazolidinediones: HR 0.62 (95% CI 0.50-0.76)
• Insulin: HR 0.58 (95% CI 0.49-0.67)

Along with the limitations noted by Drucker, the lack of individual patient-level data precluded the researchers from evaluating cancer-specific mortality and outcomes based on the specific dose of the GLP-1 agent.