Risk of lower extremity complications with GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors in peripheral artery disease
Main finding · Major amputationResult — go to the resultHazard ratio 0.79 95 % CI 0.70–0.90Authors' conclusion
GLP-1RAs were associated with lower limb complication and mortality risks in PAD, supporting a potential vascular benefit that warrants prospective evaluation.
Study context
- Population
- Adults with PAD and T2D initiating GLP-1 RA, SGLT2i or DPP-4i (May 2013-January 2025)matched cohorts
- Exposure
- GLP-1 RA vs SGLT2i vs DPP-4i
- Outcome
- Major amputation
- Follow-up
- 3 years
Methodological detailsnationwide US electronic health records database, propensity score matched (1:1)
- Nationwide US electronic health records database
- Propensity score matched (1:1)
Main finding
As reported in the abstract
3 years
Hazard ratio
0.79
95 % CI 0.70–0.90
GLP-1RAvs SGLT2i
HR 0.79 (95 % CI 0.70–0.90)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95 % CI) | |
|---|---|---|
| Lower extremity revascularization (LER) · 3 yearsGLP-1RAvs SGLT2i | 0.82 (0.76–0.88) | |
| All-cause mortality · 3 yearsGLP-1RAvs SGLT2i | 0.71 (0.68–0.73) | |
| 0.512Hazard ratio (log scale) |
Subgroups: symptomatic PAD and prior lower extremity revascularization (LER)
- GLP-1RA benefits remained significant in symptomatic PAD
- P < 0.05
- GLP-1RA associated with lower mortality in LER patients
- P < 0.05
Drug-level comparisons
- Semaglutide and tirzepatide showed the greatest benefit
Original publication
Risk of lower extremity complications with GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors in peripheral artery disease. Diabetes Res Clin Pract. Published 1 November 2025. doi:10.
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