For patients with diabetes who have already suffered serious limb complications, treatment choice may be critical. New evidence suggests GLP-1 RAs are associated with substantially lower risks of repeat limb events, cardiovascular complications, and death in this high-risk population.
Why Prior Limb Events Raise Long-Term Risk
People with diabetes and a history of major adverse limb events face a markedly increased risk of future amputations, cardiovascular disease, and kidney failure. Until now, evidence to guide glucose lowering therapy for secondary prevention in this group has been limited. GLP-1 RAs have demonstrated cardiovascular benefits in broader diabetes populations, but their impact in patients with established limb damage has remained unclear.
Researchers addressed this gap using nationwide data to directly compare GLP-1 RAs with dipeptidyl peptidase-4 inhibitors, a commonly used alternative class. The focus on patients with previous limb events allowed the study to examine outcomes in a cohort with substantially higher baseline risk than those included in earlier research.
Large Cohort Shows Consistent Risk Reductions
The retrospective cohort study analysed 17 288 patients with diabetes and prior major adverse limb events using data from the Taiwan National Health Insurance Research Database between 2012 and 2023. Among these patients, 1583 initiated GLP-1 RAs and 15 705 initiated DPP-4 inhibitors.
After weighting, use of GLP-1 RAs was associated with a lower risk of recurrent limb events, with a subdistribution hazard ratio of 0.90. This reduction was largely driven by fewer amputations, with a hazard ratio of 0.86. GLP-1 RAs were also linked to lower risks of major adverse cardiovascular events, with a hazard ratio of 0.62, and reduced cardiovascular death at 0.57. All-cause mortality was lower at 0.63, and progression to long term dialysis was reduced with a hazard ratio of 0.61.
Implications for Clinical Practice and Prevention
These findings suggest GLP-1 RAs may offer meaningful protective benefits beyond glucose control in patients with advanced diabetes complications. The consistent reductions across limb, cardiovascular, renal, and mortality outcomes support their preferential use for secondary prevention in people with prior limb events. As clinicians increasingly consider holistic risk reduction, GLP-1 RAs may play a central role in improving long-term outcomes for this vulnerable population.
Reference
Hsiao F et al. Glucagon-like peptide-1 receptor agonists and prior major adverse limb events in patients with diabetes. JAMA Netw Open. 2026;9(1):e2555952.
