OBJECTIVE: Despite the well-documented impact of glucagon-like peptide-1 (GLP-1) receptor agonist 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 ≥ 30kg/m) 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-GLP1 cohort using propensity scores that accounted for age, race, sex, smoking history, diabetes, Body Mass Index (BMI), medications, and other comorbidities. Covariate balance was assessed using standardized mean differences (SMD), with values <0.1 indicating adequate balance. CVI patients with 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 (HR) and 95% confidence intervals (CI) for our outcomes. Time-to-event analyses were assessed using Kaplan-Meier survival curves, with inter-cohort comparisons performed using the log-rank test. Statistical significance was set at a two-sided α of 0.05. All analyses were conducted within the TriNetX Analytics platform. 2
RESULTS: Of the 138,853 obese CVI patients included in our study, 12,874 patients (9.3%) were treated with GLP-1. After propensity score matching (PSM), each cohort consisted of 12,379 CVI patients with obesity. Following PSM, GLP-1 therapy was associated with a decreased risk of acute DVT (HR, 0.54; 95% CI, 0.42-0.71; p<0.001), PE (HR, 0.43; 95% CI, 0.27-0.66; p<0.001), venous ulcers (HR, 0.47; 95% CI, 0.33-0.66; p<0.001), and soft tissue infections (HR, 0.61; 95% CI, 0.52-0.72; p<0.001) at 1 year in obese CVI patients. 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, CVI patients treated with GLP-1 demonstrated a 4% (99.0% vs. 94.0%, p<0.001) and 9% (95.0% vs. 86.0%, p<0.001) absolute survival benefit, respectively, compared to their non-GLP-1 counterparts.
CONCLUSIONS: In obese patients with CVI, GLP-1 therapy was associated with reduced risk of venous thromboembolic events (VTE), 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.
