Differential Effect of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Lower-Extremity Amputation Outcomes in Type 2 Diabetes: A Nationwide Retrospective Cohort Study
Authors' conclusion
GLP-1RA treatment was associated with greater major amputation-free survival compared with SGLT2i in people with type 2 diabetes, particularly in high-risk subgroups. Prospective studies are needed to confirm findings and inform selection of glucose-lowering therapies for people at risk for diabetes-related amputations.
Study context
- Population
- Adults with T2D who initiated GLP-1RAs or SGLT2is between May 2013 and March 2025matched cohorts
- Participants
- 180,740 vs 180,740
- Exposure
- GLP-1 RA vs SGLT2i new users
- GLP-1RAn = 180,740
- SGLT2in = 180,740reference
- Outcome
- Major (above-ankle) amputation-free survival
- Follow-up
- 3 years
Methodological detailspropensity score matching (1:1), federated electronic health records network (TriNetX)
- Propensity score matching (1:1)
- Federated electronic health records network (TriNetX)
Main finding
As reported in the abstract
Major amputation-free survival
P = 0.001
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Major LEAs | 0.77 (0.66–0.90) | |
| Minor LEAs | 0.73 (0.63–0.84) | |
| DFUs | 0.92 (0.87–0.96) | |
| Mortality | 0.66 (0.63–0.69) | |
| Major LEAs, subgroup with peripheral artery disease | 0.68 (0.56–0.82) | |
| Major LEAs, subgroup with DFUs | 0.70 (0.58–0.84) | |
| 0.512Hazard ratio (log scale) |
Original publication
Differential Effect of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Lower-Extremity Amputation Outcomes in Type 2 Diabetes: A Nationwide Retrospective Cohort Study. Diabetes Care. Published 25 June 2025. doi:10.
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