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Published on: June 2, 2019
Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes
Fu-Chih Hsiao1,2, Tzyy-Jer Hsu1, Yu-Jui Hsieh1
1The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Importance:
Patients with diabetes and a history of major adverse limb events (MALEs) are at an increased risk of cardiovascular and limb-related complications; however, effective glucose-lowering therapies for secondary prevention in this population are limited.
Objective:
To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with reduced risk of MALEs and major adverse cardiovascular events (MACE) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and prior MALEs.
Design, Setting, And Participants:
This retrospective, nationwide cohort study used data from the Taiwan National Health Insurance Research Database from October 2012 to December 2023. Patients with diabetes and a history of MALE who initiated GLP-1 RAs or DPP-4 inhibitors were included. MALEs were defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation.
Exposures:
Initiation of GLP-1 RAs (liraglutide, dulaglutide, or semaglutide) vs DPP-4 inhibitors.
Main Outcomes And Measures:
The primary outcome was a composite of lower limb revascularization and nontraumatic major and minor amputation. The secondary outcomes were MACEs (cardiovascular death, ischemic stroke, and myocardial infarction), all-cause mortality, and progression to long-term dialysis. A new-user, active-comparator design with inverse probability of treatment weighting was employed.
Results:
Among 17 288 patients (mean [SD] age, 70.7 [12.0] years; 10 010 male [57.9%]), 1583 initiated GLP-1 RAs and 15 705 initiated DPP-4 inhibitors. After weighting, the use of GLP-1 RAs was associated with a lower risk of MALEs (subdistribution hazard ratio [SHR], 0.90; 95% CI, 0.83-0.97), primarily due to a marked reduction in amputation (SHR, 0.86; 95% CI, 0.75-0.98). GLP-1 RAs were also associated with reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR 0.63; 95% CI, 0.60-0.66), and progression to dialysis (SHR, 0.61; 95% CI, 0.54-0.70).
Conclusions And Relevance:
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.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce major adverse limb events (MALEs) and cardiovascular events in diabetic patients with prior MALEs compared to dipeptidyl peptidase-4 (DPP-4) inhibitors.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Nephrology
Background:
- Patients with diabetes and a history of major adverse limb events (MALEs) face elevated risks of cardiovascular and limb complications.
- Effective glucose-lowering therapies for secondary prevention in this high-risk group are limited.
Purpose of the Study:
- To compare the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing MALEs and major adverse cardiovascular events (MACE) in diabetic patients with prior MALEs.
Main Methods:
- A retrospective, nationwide cohort study utilizing the Taiwan National Health Insurance Research Database (October 2012 - December 2023).
- Included patients with diabetes and a history of MALE who initiated GLP-1 RAs (liraglutide, dulaglutide, semaglutide) or DPP-4 inhibitors.
- Employed a new-user, active-comparator design with inverse probability of treatment weighting.
Main Results:
- GLP-1 RA use was associated with a lower risk of MALEs (SHR, 0.90; 95% CI, 0.83-0.97), driven by reduced amputation rates (SHR, 0.86; 95% CI, 0.75-0.98).
- GLP-1 RAs also demonstrated reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR, 0.63; 95% CI, 0.60-0.66), and kidney disease progression (SHR, 0.61; 95% CI, 0.54-0.70).
Conclusions:
- GLP-1 RAs significantly lower the risk of recurrent limb events, cardiovascular events, mortality, and kidney disease progression compared to DPP-4 inhibitors in diabetic patients with prior MALEs.
- Findings support the preferential use of GLP-1 RAs for secondary prevention in this vulnerable population.
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