GLP-1 drugs may protect limbs in diabetes with PAD

Clinical takeaway: In patients with type 2 diabetes and peripheral artery disease, GLP-1 receptor agonists may be worth considering for more than glycemic control or weight loss. These real-world data suggest potential long-term limb and survival benefits, especially in patients with chronic limb-threatening ischemia or obesity.

Patients with both type 2 diabetes and peripheral artery disease (PAD) face high risks of cardiovascular events, functional decline, revascularization, limb loss, and death, yet few medications directly improve PAD-specific outcomes. Current pharmacologic treatment largely focuses on reducing cardiovascular risk, while limb-directed options remain limited.

GLP-1 receptor agonist use was associated with lower five-year rates of death, hospitalization, revascularization, and amputation in patients with type 2 diabetes and PAD, according to a retrospective cohort study.

Researchers compared adults with type 2 diabetes and PAD who had repeated GLP-1 receptor agonist prescriptions with similar patients treated with metformin and no GLP-1 receptor agonist exposure. The main analysis included 2133 patients in each group.

At five years, GLP-1 receptor agonist therapy was associated with lower all-cause mortality and fewer hospitalizations than metformin, including a 26% relative reduction in mortality.

The limb-related findings may be most relevant to PAD care. Compared with matched patients receiving metformin, patients receiving GLP-1 receptor agonists had lower rates of revascularization, major amputation, and minor amputation. Revascularization occurred in 4.69% versus 7.27% of patients, major amputation in 2.30% versus 4.36%, and minor amputation in 4.03% versus 6.42%. Rates of myocardial infarction, stroke, major adverse cardiovascular events, and major adverse kidney events were similar between groups.

The signal was strongest in patients at higher baseline risk. Among those with chronic limb-threatening ischemia, GLP-1 receptor agonist use was associated with lower mortality, hospitalization, revascularization, major amputation, and minor amputation. In patients with BMI of 30 or higher, use was linked to fewer hospitalizations and lower amputation risk.

That pattern points to a broader prescribing lens. In patients with type 2 diabetes and PAD, GLP-1 receptor agonists may offer potential vascular and limb benefits in addition to effects on glucose and weight. Limb risk, prior revascularization, chronic limb-threatening ischemia, obesity, and hospitalization history may be relevant when choosing glucose-lowering or weight-loss therapy, not just A1c or weight goals.

“Given the magnitude and consistency of benefit, particularly in high-risk patients with chronic limb-threatening ischemia, GLP-1 receptor agonists should be considered not only for glycemic or weight management but also as disease-modifying therapies with potential to improve long-term vascular and limb outcomes in peripheral artery disease,” the study authors wrote.

Source: Rosenzveig A, et al. (2026 July 1) J Am Heart Assoc. Long-term outcomes of glucagon-like peptide-1 receptor agonists in patients with peripheral artery disease and type 2 diabetes