Glucagon-like peptide-1 receptor agonists are associated with fewer venous thromboembolic events and limb complications in obese patients with chronic venous insufficiency.
GLP-1 therapy may be associated with a reduced risk of venous complications and improved survival in obese patients with chronic venous insufficiency.
Where it sits
this study against the rest of the albiglutide corpusSummary and findings
This study assessed the association between glucagon-like peptide-1 (GLP-1) therapy and outcomes in obese patients with chronic venous insufficiency (CVI), focusing on risks of deep vein thrombosis (DVT), pulmonary embolism (PE), venous leg ulcers, cellulitis, and all-cause mortality. GLP-1 therapy was associated with a decreased risk of these outcomes at 1 year and 3 years following diagnosis. The study utilized a retrospective cohort design with propensity score matching.
Abstract
<h4>Objective</h4>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).<h4>Methods</h4>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/m<sup>2</sup>) 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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Background
This study addresses the relationship between glucagon-like peptide-1 receptor agonist (GLP-1) therapy and venous disease outcomes in obese patients with chronic venous insufficiency (CVI). Previous research has established the impact of GLP-1 therapy on obesity and diabetes, but its effects on venous disease outcomes remain unclear. Understanding this relationship is important due to the potential implications for managing venous complications in this population.
Methods
A retrospective multicenter cohort study was conducted using the TriNetX US Collaborative Network. The study included adult patients (≥40 years) who were obese (BMI ≥30 kg/m²) and diagnosed with CVI between 2016 and 2025. Patients treated with GLP-1 therapy were matched 1:1 to a non-GLP-1 cohort based on propensity scores. The primary outcome was acute DVT risk at 1-year and 3-year follow-up, with secondary outcomes including PE, venous ulcers, soft-tissue infections, and all-cause mortality.
Results
Of the 138,853 obese patients with CVI, 12,874 (9.3%) were treated with GLP-1s. After matching, each cohort had 12,379 patients. GLP-1 therapy was associated with a decreased risk of acute DVT (HR, 0.54; 95% CI, 0.42-0.71; P < .001) and other complications at 1 year. The association was sustained at the 3-year follow-up, with significant absolute survival benefits observed at both time points.
Interpretation
The findings suggest that GLP-1 therapy may reduce the risk of venous thromboembolic events and improve survival in obese patients with CVI. While the results are statistically significant, the clinical significance should be carefully considered, especially given the retrospective nature of the study and potential confounding factors. The study highlights the need for further research to confirm these associations and explore the mechanisms involved.
Key findings
- HR for acute DVT risk at 1 year was 0.54; 95% CI, 0.42-0.71; P < .001.
- HR for PE at 1 year was 0.43; 95% CI, 0.27-0.66; P < .001.
- HR for venous ulcers at 1 year was 0.47; 95% CI, 0.33-0.66; P < .001.
- HR for soft-tissue infections at 1 year was 0.61; 95% CI, 0.52-0.72; P < .001.
- At 1 year, absolute survival benefit was 4% (99.0% vs 94.0%; P < .001).
- At 3 years, absolute survival benefit was 9% (95.0% vs 86.0%; P < .001).
Limitations
- retrospective study design
- propensity score matching may not account for all confounders
- findings may not be generalizable beyond the studied population
- short follow-up period for long-term outcomes