Glucagon-like peptide-1 receptor agonists are associated with fewer venous thromboembolic events and limb complications in obese patients with chronic venous insufficiency.

OBJECTIVE: Despite the well-documented impact of glucagon-like peptide-1 receptor agonist (GLP-1) therapy on obesity and diabetes, and the known risk factors for chronic venous insufficiency, the relationship between GLP-1 use and venous disease outcomes remains poorly understood. This study aims to assess the association between GLP-1 therapy and the risk of deep vein thrombosis (DVT), pulmonary embolism (PE), venous leg ulcers, cellulitis, and all-cause mortality at 1 year and 3 years following diagnosis in obese patients with chronic venous insufficiency (CVI).

METHODS: We conducted a retrospective multicenter cohort study using the TriNetX US Collaborative Network to identify adult patients (≥40 years) who were obese (body mass index ≥30 kg/m2) and had a diagnosis of CVI between 2016 and 2025. Patients who were started on GLP-1 therapy were matched 1:1 to a non-GLP-1 cohort using propensity scores that accounted for age, race, sex, smoking history, diabetes, body mass index, medications, and other comorbidities. Covariate balance was assessed using standardized mean differences, with values <0.1 indicating adequate balance. Patients with CVI and a prior history of DVT and PE were excluded from the study. The primary outcome was acute DVT risk at 1-year and 3-year follow-up after a CVI diagnosis. Secondary outcomes included PE, venous ulcers, associated soft-tissue infections, and all-cause mortality at both time points. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for our outcomes. Time-to-event analyses were assessed using Kaplan-Meier survival curves, with intercohort comparisons performed using the log-rank test. Statistical significance was set at a two-sided α of .05. All analyses were conducted within the TriNetX Analytics platform.

RESULTS: Of the 138,853 obese patients with CVI included in our study, 12,874 patients (9.3%) were treated with GLP-1s. After propensity score matching, each cohort consisted of 12,379 patients with CVI and obesity. Following propensity score matching, GLP-1 therapy was associated with a decreased risk of acute DVT (HR, 0.54; 95% CI, 0.42-0.71; P < .001), PE (HR, 0.43; 95% CI, 0.27-0.66; P < .001), venous ulcers (HR, 0.47; 95% CI, 0.33-0.66; P < .001), and soft-tissue infections (HR, 0.61; 95% CI, 0.52-0.72; P < .001) at 1 year in patients with CVI and obesity. The association between GLP-1 therapy and reduced risk of developing DVT, PE, venous ulcers, and soft-tissue infections was sustained at the 3-year follow-up. At both 1- and 3-year follow-up, patients with treated with GLP-1 demonstrated a 4% (99.0% vs 94.0%; P < .001) and 9% (95.0% vs 86.0%; P < .001) absolute survival benefit, respectively, compared with their non-GLP-1 counterparts.

CONCLUSIONS: In obese patients with CVI, GLP-1 therapy was associated with reduced risk of venous thromboembolic events, venous leg ulcers, and soft-tissue infections, as well as improved long-term survival. These findings suggest that GLP-1 use may confer clinically protective effects in patients with CVI. Future studies are warranted to better understand the role of GLP-1 treatment in the management of venous disease.