Risk of all–cause death and pancreatic events following GLP-1 RA initiation in people with obesity or type 2 diabetes: observations from a federated research network
Authors' conclusion
GLP-1 RA use was associated with substantially reduced all-cause death but a small increased risk of acute pancreatitis, particularly during early treatment. The survival benefit was more pronounced in younger people and those with cardiometabolic comorbidities, highlighting the need for a careful risk-benefit evaluation when prescribing GLP-1 RAs in high-risk individuals.
Study context
- Population
- Adults (≥ 18 years) with obesity (BMI ≥ 30 kg/m²) or T2D (ICD-10-CM: E11), 2018–2024
- Participants
- 1,562,626 vs 18,652,572
- Exposure
- GLP-1 RA initiation vs no GLP-1 RA
- GLP-1 RA Usersn = 1,562,626
- Non-GLP-1 RA Usersn = 18,652,572reference
- Outcome
- All-cause death and a composite outcome (acute pancreatitis, chronic pancreatitis)
- Follow-up
- 1 year
Methodological detailsfederated research network (TriNetX), 1:1 propensity score matching
- Federated research network (TriNetX)
- 1:1 propensity score matching
Main finding
As reported in the abstract
Each group vs Non-GLP-1 RA UsersEstimate (95% CI)
GLP-1 RA Users
HR (all-cause death) 0.554(0.542–0.566)
GLP-1 RA Users
HR (composite acute/chronic pancreatitis) 1.062(1.023–1.102)
Observational data: associations, not effects.
Secondary outcomes
Subgroups by age
- Greater reduction in death and composite outcome among people aged < 65 years
Other subgroups (all-cause death)
- Significant interactions for all-cause death in females and in people with history of smoking, alcohol use, HF, CKD or cholelithiasis
Safety
| Outcome | HR (95% CI) | |
|---|---|---|
| Acute pancreatitis · 1 yearAfter PSM | 1.058 (1.015–1.103) | |
| 0.512Hazard ratio (log scale) |
Acute pancreatitis · 1 year
- Excess risk more pronounced in early phase (first 6 months)
Chronic pancreatitis and pancreatic cancer
- No differences in chronic pancreatitis or pancreatic cancer
Original publication
Risk of all–cause death and pancreatic events following GLP-1 RA initiation in people with obesity or type 2 diabetes: observations from a federated research network. Cardiovasc Diabetol. Published 19 November 2025. doi:10.
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