Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes.
Level 3 - non-randomized controlled study
Retrospective propensity score-matched cohort study using electronic health records
PubMed 38967919 · doi:10.1001/jamanetworkopen.2024.21305
What was done
This retrospective cohort study analyzed electronic health records from a US multicenter database of 113 million patients between March 2005 and November 2018. The study included 1,651,452 patients with type 2 diabetes and no prior obesity-associated cancers (OACs) who were prescribed GLP-1 receptor agonists (GLP-1RAs), insulins, or metformin. Propensity-score matching was used to adjust for baseline covariates. Incident first-time diagnoses of 13 OACs were evaluated over up to 15 years of follow-up using Cox proportional hazards and Kaplan-Meier analyses.
What was found
Compared with insulin, GLP-1RAs were associated with statistically significant risk reductions in 10 of 13 OACs: gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Risk reduction was not statistically significant for stomach cancer (HR, 0.73; 95% CI, 0.51-1.03), postmenopausal breast cancer, or thyroid cancer. Compared with metformin, GLP-1RAs showed no decreased risk for any cancer and were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87).
Why it matters
The findings suggest GLP-1RAs may confer substantial protective benefits against specific obesity-related malignancies compared with insulin, although they do not show an advantage over metformin.
Limits
The study is observational and retrospective, meaning unmeasured confounding, channeling bias, or differences in baseline disease severity between drug classes cannot be ruled out. Medication adherence, dose exposure, and duration of use were not detailed in the abstract.
Cited by
- partial Data indicates an increased risk signal for kidney cancer associated with GLP-1 receptor agonist medications.