GLP- 1 Receptor Agonists in Patients with Cancer are Associated with Reduced All-Cause Mortality and Hospitalization

Abstract

Background: GLP- 1 RA 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-1 RA 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-1 RA in patients with active cancer are limited.

Methods: Using TriNetX, a global database comprising over 120 million patients, we identified an overall cohort of 3747 patients with type 2 diabetes who received GLP-1 RA within 3 months of starting systemic therapy and identified 52,061 patients receiving metformin in the same timeframe as a control cohort. Additional sub-analyses stratified patients by hemoglobin A1c 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-1 RA had significantly reduced mortality in both the overall monotherapy setting (HR: 0.875, 95% CI: (0.778-0.985), p=0.0268) and the new start setting (HR: 0.786 , 95% CI: (0.662-0.934), p= 0.0062) cohorts. Secondary analyses found lower rates of all-cause hospitalization, sepsis, major adverse cardiovascular events, pulmonary embolism, and pneumonia in patients on GLP-1 RA. Sub-analyses stratified by BMI and A1c did not meet statistical significance.

Conclusions: Patients with diabetes and cancer who received GLP-1 RA experienced superior survival outcomes and reduced rates of hospitalization compared to patients receiving metformin. Additionally, patients already on metformin and newly started on GLP-1 RA demonstrated superior survival outcomes compared to patients newly started on insulin. Further prospective, well-controlled studies are needed to evaluate the benefits of GLP-1 RA in patients with diabetes and cancer.

Keywords: GLP-1RA; cancer; dulaglutide; exenatide; liraglutide; semaglutide; survival; tirzepatide.