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Observational Study Links GLP-1 Receptor Agonist Use to Improved Survival and Reduced Recurrence in Certain Breast Cancer Patients

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GLP-1 Drugs Tied to Better Survival in Early-Stage Breast Cancer Patients With Obesity or Diabetes

A large retrospective study found an association between GLP-1 receptor agonist (GLP-1RA) use and improved survival in women with early-stage breast cancer who also had obesity or type 2 diabetes. However, the authors caution that randomized clinical trials are needed before these drugs can be incorporated into cancer care.

Study Design and Methods

Researchers analyzed electronic health records from the TriNetX US Collaborative Network, which includes data from 68 healthcare organizations. The study included 841,831 adult women diagnosed with stage I, II, or III breast cancer between April 1, 2006, and April 1, 2023. Patients with stage IV breast cancer, prior malignant neoplasms, or metastatic disease were excluded.

GLP-1RA use was defined as at least two prescriptions filled in the six months prior to or any time after breast cancer diagnosis. The sample was stratified into two groups for separate analyses:

  • Obesity cohort: Patients with obesity but without type 2 diabetes (T2D).
  • Type 2 diabetes cohort: Patients with T2D.

The primary outcome was all-cause mortality, and the secondary outcome was recurrence-free survival (RFS) over a 10-year follow-up. Researchers used 1:1 propensity score matching and Cox proportional hazards regression to estimate hazard ratios.

Key Findings by Cohort

Obesity Cohort
  • Comparison: GLP-1RA use (n=1,610 after matching) versus non-use.
  • All-cause mortality: Associated with a lower risk. The five-year survival probability was 97.4% for GLP-1RA users and 93.2% for non-users.
  • Recurrence-free survival: Associated with a lower risk of metastatic recurrence. The five-year probability was 96% for GLP-1RA users and 91.3% for non-users.
Type 2 Diabetes Cohort (GLP-1RAs vs. Insulin or Metformin)
  • Comparison: GLP-1RA use (n=2,323 after matching) versus use of insulin or metformin.
  • All-cause mortality: Associated with a lower risk. The five-year survival probability was 96.9% for GLP-1RA users and 82.3% for insulin/metformin users.
  • Recurrence-free survival: Associated with a lower risk. The five-year probability was 97.4% for GLP-1RA users and 93.4% for insulin/metformin users.
Type 2 Diabetes Cohort (GLP-1RAs vs. SGLT2 Inhibitors)
  • Comparison: GLP-1RA use (n=4,052 after matching) versus use of SGLT2 inhibitors.
  • All-cause mortality and recurrence-free survival: Unadjusted analyses showed no statistically significant difference between the two drug classes. Adjusted analyses suggested a lower hazard associated with GLP-1RA use, but the association was less pronounced than in the comparison with insulin/metformin. In postmenopausal subgroup and 12-month landmark analyses, the protective associations versus SGLT2 inhibitors were not sustained.

Study Limitations

The authors acknowledged several limitations:

  • Its retrospective, observational design prevents the establishment of causality.
  • Reliance on structured electronic health record data and diagnostic codes.
  • Potential residual confounding factors.
  • Lack of data on patient medication adherence and weight changes.
  • Grouping of different types of GLP-1RAs as a single exposure.
  • Significant administrative censoring of data around the five-year mark, limiting the precision of long-term survival estimates.