Diabetes Obes MetabHeart & CardiovascularMeta-AnalysisDecember 22, 2025

Impact of glucagon-like peptide-1 receptor agonism-based therapies on limb outcomes in peripheral artery disease and type 2 diabetes: An updated systematic review and meta-analysis.

Dutta D, Mahajan K, Kamrul-Hasan ABM, Mahajan N, Sharma M, Vohra S

Key Finding

GLP-1 medications reduce major limb complications by 30-34% in people with peripheral artery disease and diabetes, while cutting amputation risk in half across broader diabetes populations.

What This Study Found

Think of peripheral artery disease (PAD) like having clogged pipes in your legs - blood flow gets restricted, leading to serious complications like amputations and the need for surgical procedures to restore circulation. This massive analysis looked at over 2 million patients across 17 studies to see if GLP-1 medications (like Ozempic and Wegovy) could help protect limbs in people with diabetes and PAD. The researchers created two groups: one focused specifically on PAD patients (352,743 people) and another looking at broader diabetes populations (1.76 million people). In the PAD-specific group, GLP-1 medications reduced major adverse limb events by 34% and significantly cut the need for revascularization procedures (surgical interventions to restore blood flow) by 15%. Perhaps most remarkably, these medications reduced the risk of death by 45% in PAD patients - imagine if a treatment for clogged arteries in your legs also dramatically improved your overall survival odds. In the broader diabetes population, the limb benefits were equally impressive, with amputation risk dropping by 42% - meaning if 100 diabetes patients typically needed amputations, only 58 would need them with GLP-1 treatment.

Statistics Decoded

OR 0.66 for major limb events means 34% lower risk - like reducing bad outcomes from 100 to 66 per 1000 patients. OR 0.55 for death means 45% lower mortality risk - a huge survival benefit that probably wasn't just luck (p=0.0008). The revascularization OR of 0.85 means 15% fewer patients needed surgical procedures to restore blood flow (p<0.001 - definitely not coincidence). In the diabetes group, OR 0.58 for amputations translates to 42% fewer amputations, and the I2=0% means all studies agreed on this finding. The high I2 values (94-97%) in some PAD analyses mean there was significant variation between studies, suggesting results should be interpreted cautiously.

Why This Matters

This research reveals that GLP-1 medications aren't just diabetes and weight-loss drugs - they're powerful limb-savers that could prevent thousands of amputations and vascular surgeries in high-risk patients. For doctors treating diabetes patients with circulation problems, this evidence suggests GLP-1 therapies should be strongly considered not just for blood sugar control, but as a limb preservation strategy.

Original Abstract

Glucagon-like peptide-1 receptor agonism (GLP1RA)-based therapies (GLP1RA-BTs) form the cornerstone for managing type 2 diabetes (T2D) and obesity. However, their impact on limb-specific outcomes in peripheral artery disease (PAD) remains unclear. This systematic-review and meta-analysis evaluated the safety and efficacy of GLP1RA-BTs on limb outcomes in PAD and T2D. Electronic databases were searched for studies involving GLP1RA-BTs in PAD and/or T2D. Primary outcome was the major adverse limb events (MALEs). Secondary outcomes were all-cause mortality, revascularization, amputation, major adverse cardiovascular events (MACE), cardiovascular mortality, myocardial infarction (MI), stroke, hospitalization for heart-failure (HHF), and amputations. Analyses were performed separately for studies exclusively enrolling patients with PAD (PAD cohort) and for those in broader T2D populations reporting limb outcomes but not limited to PAD, in which PAD comprised <15% of participants (T2D cohort). Data from 10 studies for PAD cohort (352 743 patients) and 7 studies for T2D cohort (1 759 799 patients) were analysed. In PAD cohort, MALE [OR 0.66 (0.44, 1.00); p = 0.05; I2 = 94%], all-cause mortality [OR 0.55 (0.38, 0.78); p = 0.0008; I2 = 97%], MACE [OR 0.68 (0.52, 0.88); p = 0.004; I2 = 85%], and MI [OR 0.68 (0.51, 0.91); p = 0.009; I2 = 42%] were lower in patients on GLP1RA-BTs compared to controls. In the PAD cohort, need for revascularization was significantly lower in GLP1RA-BTs than in controls [OR 0.85 (0.80, 0.90); p < 0.001; I2 = 0%]. In the T2D cohort, MALE [OR 0.70 (0.57, 0.85); p = 0.0005; I2 = 0%], amputations [OR 0.58 (0.48, 0.69); p < 0.001; I2 = 0%], and all-cause mortality [OR 0.55 (0.43, 0.69); p < 0.001; I2 = 85%] were significantly lower in GLP1RA-BT compared to controls. GLP1RA-BTs are beneficial in PAD, especially in reducing the need for revascularization.