Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes
Main finding · MALEsResult — go to the resultSubdistribution hazard ratio 0.90 95% CI 0.83–0.97Authors' conclusion
In this nationwide cohort study of patients with diabetes and prior MALEs, treatment with GLP-1 RAs was associated with significantly lower risks of recurrent limb events, cardiovascular events, all-cause mortality, and kidney disease progression compared with DPP-4 inhibitors. These findings support the preferential use of GLP-1 RAs for secondary prevention in this high-risk population.
Study context
- Population
- Patients with diabetes and a history of MALE (chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation), Taiwan National Health Insurance Research Database, October 2012 to December 2023; mean (SD) age 70.7 (12.0) years, 57.9% male
- Participants
- 17,288 patients
- Exposure
- GLP-1 RA vs DPP-4i initiation
- Outcome
- Composite of lower limb revascularization and nontraumatic major and minor amputation (major adverse limb events (MALEs))
Methodological detailsnationwide, new-user, active-comparator design, inverse probability of treatment weighting
- Nationwide
- New-user, active-comparator design
- Inverse probability of treatment weighting
Main finding
MALEs
Subdistribution hazard ratio
0.90
95% CI 0.83–0.97
GLP-1 RAsvs DPP-4 inhibitors
subdistribution HR 0.90 (95% CI 0.83–0.97)
As reported in the abstract
Observational data: associations, not effects.
Secondary outcomes
| Outcome | Estimate | |
|---|---|---|
| AmputationGLP-1 RAsvs DPP-4 inhibitors | subdistribution HR 0.86 (95% CI 0.75–0.98) | |
| MACE (CV death, ischemic stroke, MI)GLP-1 RAsvs DPP-4 inhibitors | HR 0.62 (95% CI 0.58–0.65) | |
| Cardiovascular deathGLP-1 RAsvs DPP-4 inhibitors | HR 0.57 (95% CI 0.53–0.61) | |
| All-cause mortalityGLP-1 RAsvs DPP-4 inhibitors | HR 0.63 (95% CI 0.60–0.66) | |
| Progression to long-term dialysisGLP-1 RAsvs DPP-4 inhibitors | subdistribution HR 0.61 (95% CI 0.54–0.70) | |
| 0.512Ratio (log scale) |
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes. JAMA Netw Open. Published 2 January 2026. doi:10.
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