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

Aditya Mahadevan1, Aidan Vosooghi2, Jagmeet S Arora3

  • 1Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

The Journal of Clinical Endocrinology and Metabolism
|January 3, 2026
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise for patients with diabetes and active cancer, significantly reducing mortality and hospitalization rates compared to metformin. Further research is warranted to confirm these survival benefits.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may decrease cancer incidence.
  • Preclinical data suggest GLP-1 RAs inhibit solid tumor progression by downregulating proliferation pathways and improving glycemic control.
  • Limited studies exist on GLP-1 RA effects in patients with active cancer.

Purpose of the Study:

  • To evaluate the impact of GLP-1 RAs on survival and clinical outcomes in patients with type 2 diabetes and active cancer.
  • To compare GLP-1 RA effectiveness against metformin in a large patient cohort.
  • To explore GLP-1 RA benefits in specific patient subgroups.

Main Methods:

  • Utilized TriNetX, a global database of over 120 million patients.
  • Identified 3,747 patients with type 2 diabetes on GLP-1 RAs and 52,061 on metformin, initiating systemic therapy within 3 months.
  • Conducted sub-analyses based on hemoglobin A1c, obesity, and new GLP-1 RA initiation.

Main Results:

  • GLP-1 RA use was associated with significantly reduced mortality in overall (HR: 0.875) and new-start (HR: 0.786) cohorts.
  • Secondary analyses revealed lower rates of hospitalization, sepsis, MACE, PE, and pneumonia with GLP-1 RAs.
  • Stratified sub-analyses by BMI and A1c did not reach statistical significance.

Conclusions:

  • GLP-1 RAs improved survival and reduced hospitalizations in diabetic cancer patients compared to metformin.
  • Newly initiated GLP-1 RAs showed superior survival versus new insulin users.
  • Prospective studies are essential to confirm GLP-1 RA benefits in this population.
Keywords:
GLP-1RAcancerdulaglutideexenatideliraglutidesemaglutidesurvivaltirzepatide

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