Benefits of Glucagon-like peptide (GLP)-1 receptor agonists on 5-year risk of major amputation, all-cause mortality, myocardial infarction, and ischemic stroke in patients with chronic limb-threatening ischemia (CLTI)

Dec 18, 2025Vascular medicine (London, England)

GLP-1 receptor drugs and their effects on 5-year risk of major amputation, death, heart attack, and stroke in people with severe limb blood flow problems

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Abstract

Among 139,173 patients with type 2 diabetes and chronic limb-threatening ischemia, GLP-1 receptor agonist users had a lower rate of major amputation (hazard ratio: 0.745).

GLP-1 receptor agonist users demonstrated a 30% reduction in the risk of all-cause mortality (hazard ratio: 0.7).
Users also had a 16% lower risk of myocardial infarction (hazard ratio: 0.838).
No significant difference in the risk of ischemic stroke was observed (hazard ratio: 0.969).
The study utilized a retrospective cohort design and matched 15,743 patients in each treatment group.

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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM), but their effect on the risk of cardiovascular events and amputation in patients with chronic limb-threatening ischemia (CLTI) remains underexplored. This retrospective cohort study evaluated the association between GLP-1RA use and the 5-year risk of major amputation, all-cause mortality, and cardiovascular events in diabetic patients with CLTI.

METHODS: The TriNetX real-world clinical data platform was used to identify patients with T2DM and CLTI, categorized by GLP-1RA prescription records. Propensity score matching was applied based on demographics, comorbidities, concurrent medications, and laboratory values. Cox proportional hazards, Kaplan-Meier curves, and the log-rank test were used for analysis.

RESULTS: Among 139,173 patients with T2DM and CLTI, 17,306 patients were GLP-1RA users and 121,867 were non-GLP-1RA users. Following propensity score matching, 15,743 patients remained in each group (91% match rate). The mean age was 65.4 ± 11 years and 58.9% were men. The mean follow-up duration was 753.7 days. GLP-1RA users had a significantly lower rate of major amputation (hazard ratio [HR]: 0.745; 95% CI: 0.679-0.816; log-rank< 0.001), all-cause mortality (HR: 0.7; 95% CI: 0.663-0.738; log-rank< 0.001), and myocardial infarction (MI) (HR: 0.838; 95% CI: 0.792-0.886; log-rank< 0.001). There was no difference in the risk of ischemic stroke (HR: 0.969; 95% CI: 0.906-1.036; log-rank= 0.353). p p p p

CONCLUSION: The use of GLP-1RA medications is associated with a significant decrease in the 5-year risk of major amputations, all-cause mortality, and MI in diabetic patients with CLTI.

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Benefits of Glucagon-like peptide (GLP)-1 receptor agonists on 5-year risk of major amputation, all-cause mortality, myocardial infarction, and ischemic stroke in patients with chronic limb-threatening ischemia (CLTI)

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