Long‐term delirium and survival outcomes in patients treated with GLP ‐1 receptor agonists versus metformin in type 2 diabetes: A population‐based cohort study
Main finding · Incident deliriumResult — go to the resultAdjusted hazard ratio 0.98 95% CI 0.94–1.02Authors' conclusion
GLP-1 RA use was initially associated with a lower risk of delirium, but this association reversed over time. Subgroup variations suggest individualised treatment considerations. Metformin remains a preferred option given its stable cognitive and survival benefits.
Study context
- Population
- Adults (≥18 years) with T2D initiating GLP-1 RAs or metformin, TriNetX network (≈85% U.S.-based healthcare organisations)matched cohort
- Participants
- 63,096 vs 63,096
- Exposure
- GLP-1 RAs vs metformin
- GLP-1 RAsn = 63,096
- Metforminn = 63,096reference
- Outcome
- Incident delirium
Methodological detailspropensity-score matched, 1:1 propensity score matching (PSM), TriNetX global federated research network
- Propensity-score matched
- 1:1 PSM
- TriNetX global federated research network
Main finding
As reported in the abstract
overall
Adjusted hazard ratio
0.98
95% CI 0.94–1.02
P = 0.3628
GLP-1 RAsvs Metformin
aHR 0.98 (95% CI 0.94–1.02); P = 0.3628
Observational data: associations, not effects.
Secondary outcomes
| Outcome | GLP-1 RAs | AHR (95% CI) | P value | |
|---|---|---|---|---|
| All-cause mortalityHigher in long-term hazard | 6.28% | 1.16 (1.12–1.21) | P < 0.001 | |
| 0.512Adjusted hazard ratio (log scale) |
Incident delirium, first 5 years
- Protective in the first 5 years, AHR (95% CI); p
- 0.89 (0.86-0.92); p < 0.0001
- Time-dependent Cox model
- PSM 1:1
Incident delirium, 5–10 years · between 5 and 10 years
- Increased delirium risk between 5 and 10 years, AHR (95% CI); p
- 1.15 (1.04-1.26); p = 0.0046
- Time-dependent Cox model
- PSM 1:1
Incident delirium by subgroup
- Lower delirium risk with GLP-1 RAs in middle-aged patients (40-79 years) and those with HbA1c <7.5%
- Higher risk in Asian and Native Hawaiian/Pacific Islander populations
- Interpret with caution: relatively small subgroup sizes; Asian and Native Hawaiian/Pacific Islander patients <5% of cohort
All-cause mortality
- Mortality risk lower in absolute terms for GLP-1 RAs
Original publication
Long‐term delirium and survival outcomes in patients treated with GLP ‐1 receptor agonists versus metformin in type 2 diabetes: A population‐based cohort study. Diabetes Obes Metab. Published 7 May 2025. doi:10.
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