GLP-1 receptor agonists in patients with cancer are associated with reduced all-cause mortality and hospitalization

CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been reported to decrease cancer incidence, but less is known about their potential in patients with active cancer. Preclinical studies have demonstrated that GLP-1RAs inhibit progression of solid tumor malignancies via downregulation of cellular proliferation pathways and improved glycemic control. Despite these promising findings, studies characterizing the effects of GLP-1RAs in patients with active cancer are limited. OBJECTIVE: To evaluate the effects of GLP-1RAs on mortality and hospitalization in patients with type 2 diabetes and active cancer compared to those receiving metformin. METHODS: Using TriNetX, a global database comprising more than 120 million patients, we identified an overall cohort of 3747 patients with type 2 diabetes who received GLP-1RAs within 3 months of starting systemic therapy and identified 52 061 patients receiving metformin in the same timeframe as a control cohort. Additional subanalyses stratified patients by glycated hemoglobin A1c (HbA1c) range, obesity, and by participants "newly started" on their first instance of GLP-1 RA within 3 months of starting cancer treatment. RESULTS: Patients receiving GLP-1RAs had significantly reduced mortality both in the overall monotherapy setting (hazard ratio [HR]: 0.875; 95% CI, 0.778-0.985; P = .0268) and the new-start setting (HR: 0.786; 95% CI, 0.662-0.934; P = .0062) cohorts. Secondary analyses found lower rates of all-cause hospitalization, sepsis, major adverse cardiovascular events, pulmonary embolism, and pneumonia in patients on GLP-1RAs. Subanalyses stratified by body mass index and HbA1c did not meet statistical significance. CONCLUSION: Patients with diabetes and cancer who received GLP-1RAs experienced superior survival outcomes and reduced rates of hospitalization compared to patients receiving metformin. Additionally, patients already on metformin and newly started on GLP-1RAs demonstrated superior survival outcomes compared to patients newly started on insulin. Further prospective, well-controlled studies are needed to evaluate the benefits of GLP-1RAs in patients with diabetes and cancer.