SGLT2is Versus Metformin for Delirium Prevention in Type 2 Diabetes: A Real-World, Head- to-Head Comparative Study
Authors' conclusion
This first head-to-head, real-world study suggests that SGLT2is may offer superior protection against delirium compared with metformin in patients with T2D, especially in high-risk populations. These findings support the inclusion of cognitive outcomes in diabetes treatment decisions and suggest a potential shift in first-line therapy strategies.
Study context
- Population
- Adults with T2D initiating an SGLT2i or metformin, 2005 to 2025before matching
- Participants
- 857,171 adults
- Exposure
- SGLT2i vs metformin
- SGLT2in = 88,012
- Metforminn = 769,159reference
- Outcome
- Incident delirium
Methodological detailsreal-world, head-to-head, propensity score matching (1:1), TriNetX global health research network
- Real-world
- Head-to-head
- Propensity score matching (1:1)
- TriNetX global health research network
Main finding
As reported in the abstract
Adjusted hazard ratio (95% CI)P value
SGLT2ivs Metformin
0.91(0.87–0.95)
P < 0.001- Metformin vs SGLT2i
- Absolute risk reduction (ARR) 5.03%
Observational data: associations, not effects.
Secondary outcomes
| Outcome | Estimate | P value |
|---|---|---|
| All-cause mortalitySGLT2i vs Metformin · lower with SGLT2i · propensity-score matched | ARR 9.23% | |
| All-cause mortalityBetween SGLT2i and Metformin · propensity-score matched | aHR 0.85 (95% CI 0.87–0.88) | P < 0.001 |
Delirium in subgroups (aged ≥80 years, males, insulin or sedative users)
- Most pronounced benefits in adults aged ≥80 years (aHR)
- 0.83, P < 0.0001
- Most pronounced benefits also in males and high-risk subgroups using insulin or sedatives
Original publication
SGLT2is Versus Metformin for Delirium Prevention in Type 2 Diabetes: A Real-World, Head- to-Head Comparative Study. Diabetes Care. Published 28 May 2025. doi:10.
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