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Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data
Lindsey Wang1, QuanQiu Wang2, Li Li3,4
1Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States.
Background:
Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status.
Methods:
This retrospective cohort included patients with type 2 diabetes mellitus who were prescribed GLP-1RAs or other nonglucagon-like peptide-1 receptor agonist antidiabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other nonglucagon-like peptide-1 receptor agonist antidiabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio and 95% confidence interval calculated.
Results:
The study population comprised 1 636 056 eligible patients including 167 091 prescribed GLP-1RAs and 1 468 965 prescribed other antidiabetes medications. GLP-1RAs were associated with a statistically significant decreased risk for pancreatic cancer incidence compared with each of 6 nonglucagon-like peptide-1 receptor agonist antidiabetes medications with hazard ratios ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies.
Conclusions:
GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with type 2 diabetes mellitus. Further studies and trials are needed to explore mechanisms and confirm causal effects.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show a reduced risk of pancreatic cancer in type 2 diabetes patients. This protective effect was more pronounced in individuals with obesity and tobacco use disorder.
Area of Science:
- Endocrinology
- Oncology
- Diabetes Mellitus Research
Background:
- Limited and inconsistent data exist on the impact of GLP-1RAs on pancreatic cancer incidence.
- This study investigates the association between GLP-1RAs and pancreatic cancer risk in a real-world setting.
Purpose of the Study:
- To evaluate the association of GLP-1RAs, alone and in combination, with incident pancreatic cancer risk.
- To stratify this risk by obesity and smoking status in patients with type 2 diabetes mellitus.
Main Methods:
- Retrospective cohort study of patients with type 2 diabetes mellitus (2013-2019).
- Propensity-score matched analysis comparing GLP-1RAs with other antidiabetes medications.
- Subgroup analyses for obesity and tobacco use disorder; comparison of combination vs. monotherapies.
Main Results:
- GLP-1RAs were associated with a statistically significant decreased risk of pancreatic cancer (HRs 0.42-0.82) compared to other antidiabetes medications.
- Risk reduction was greater in patients with obesity and tobacco use disorder.
- GLP-1RA combination therapies showed lower pancreatic cancer risk than monotherapies.
Conclusions:
- GLP-1RAs are linked to reduced pancreatic cancer incidence in patients with type 2 diabetes mellitus.
- Further research is warranted to elucidate mechanisms and confirm causality.
