Glucagon-like Peptide-1 receptor agonists are not associated with increased risk of pancreatic cancer: A systematic review and meta-analysis.
Gaetano Lauri, Paolo Giorgio Arcidiacono, Antonio Facciorusso et al.
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In 30 seconds
This systematic review and meta-analysis assessed pancreatic ductal adenocarcinoma (PDAC) incidence among adults with type 2 diabetes or obesity treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). It included 60 studies—49 randomised trials and 11 observational cohorts—with 4,932,290 patients. Overall, GLP-1 RA use was not associated with increased PDAC risk; the pooled estimate was OR 0.688, 95% CI 0.575-0.824, with I 2 = 69.4%. An inverse association appeared mainly in observational cohorts and selected subgroups, but the authors call for further high-quality studies.
Key findings
- Across 60 studies and 4,932,290 patients, GLP-1 RA use was not associated with increased PDAC risk (OR 0.688, 95% CI 0.575-0.824; I 2 = 69.4%).
- An inverse association was observed mainly in observational cohorts, in overweight/obese patients with diabetes, and with exposure >52 weeks and follow-up >60 weeks.
- Meta-regression identified treatment duration and indication as significant effect modifiers.
Why it matters
The pooled evidence addresses concern about pancreatic cancer risk during GLP-1 RA treatment in adults with diabetes or obesity. The overall finding is reassuring regarding increased risk, while the inverse association should be interpreted cautiously because it was seen mainly in observational data and varied by treatment duration and indication.
What to keep in mind
Heterogeneity was substantial (I 2 = 69.4%), and the possible inverse association was mainly observed in observational cohorts; the authors state that further high-quality studies are warranted.