TOPLINE:

A new retrospective analysis suggested that GLP-1 receptor agonist use was associated with a 37% reduction in all-cause mortality compared with nonuse among patients with cancer, brain metastases, and type 2 diabetes. Similar associations were observed across several major cancer types and most GLP-1 agents.

METHODOLOGY:

• Preclinical evidence suggests that GLP-1s may have neuroprotective and anti-inflammatory effects, but clinical evidence evaluating whether GLP-1s can improve survival outcomes in patients with brain metastases remains limited.
• To assess the association between GLP-1 use and survival in patients with brain metastases and type 2 diabetes, researchers conducted a retrospective cohort study using the TriNetX Global Network, a federated database comprising 151 healthcare organizations worldwide.
• Overall, the study compared adult patients (aged ≥ 18 years) with cancer, brain metastases, and type 2 diabetes; 850 GLP-1 users were matched to 850 nonusers. GLP-1s included dulaglutide, liraglutide, and semaglutide.
• The primary outcome was all-cause mortality up to 3 years from the study index date, defined as the recorded diagnosis date of brain metastases. Subgroup analyses were conducted by primary cancer site and GLP-1 type and included comparisons with other antidiabetic agents.

TAKEAWAY:

• GLP-1 use was associated with a 37% reduction in all-cause mortality compared with nonuse (hazard ratio [HR], 0.63; P < .001) among patients with cancer, brain metastases, and type 2 diabetes.
• The association between GLP-1 use and lower mortality was also similar across major cancer types, including lung cancer (HR, 0.75), breast cancer (HR, 0.55), and melanoma (HR, 0.66).
• Among GLP-1 types, semaglutide showed the strongest association with lower mortality (HR, 0.38), followed by dulaglutide (HR, 0.75), but liraglutide showed no significant effect (HR, 0.96; 95% CI, 0.71-1.31).
• Compared with other antidiabetic agents, GLP-1 use was also associated with lower mortality.

IN PRACTICE:

“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 study authors explained.

SOURCE:

The Research Letter, from Kuan Yu Chi, MD, Albert Einstein College of Medicine, New York City, and co-authors, was published online on March 11 in JAMA Network Open.

LIMITATIONS:

The retrospective design limited causal inference, despite propensity score matching and comparable falsification endpoints. The lack of individual-level data precluded dose-response analyses, detailed assessment of concomitant systemic and radiation therapies, and evaluation of cancer-specific mortality. The restriction of 1:1 propensity score matching within TriNetX excluded substantial nonusers, limiting the generalizability of findings to patients with sufficient covariate overlap. Participating healthcare organizations within TriNetX included mostly academic hospitals, further limiting the generalizability of findings to nonacademic settings.

DISCLOSURES:

The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.