OBJECTIVE: Chronic venous leg ulcers are a prevalent and debilitating complication of chronic venous insufficiency. Up to 20% of patients with venous ulcers are diabetic and up to 50% struggle with obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an established class of agents used primarily for the treatment of type 2 diabetes and obesity. Studies have repeatedly demonstrated that their use is associated with reductions in major adverse cardiac events (MACE) and major adverse limb events (MALE), but their effects on venous ulcer healing has not yet been investigated.
METHODS: Data was sourced from the TriNetX research network, encompassing 101 health care organizations. We utilized a 1:1 propensity-matched study to compare patients with an active venous ulcer and started on GLP-1 RAs (Group 1) with those who were not started on GLP-1 RAs (Group 2). To control for differences in the cohorts, we controlled for age, race, sex, diabetes status, smoking history, and baseline weight. Outcomes included wound healing, inpatient admission, major adverse cardiovascular events (MACE), and major adverse limb events (MALE) which were identified using ICD-10 codes. Patients with arterial insufficiency defined by an abnormal ankle-brachial index were excluded.
RESULTS: We identified 381,512 patients with venous ulcers between October 1, 2022, and December 31, 2023. After propensity matching, we arrived at a study population of 38,834 matched pairs. Patients in Group 1 were found to have a higher starting mean weight (247 ± 68.2 vs 216 ± 64.2, P=.001) and hemoglobin A1c (7.7 ± 0.8 vs 7.2 ± 0.8, P<0.01). At the one-year follow-up period, Group 1 exhibited more weight loss (240 ± 65.0 vs 212 ± 63.5, P<.01), fewer non-healing ulcers (0.61% vs 0.92%, P<.01), fewer inpatient admissions for wound-related infection (18.4% vs 30.8%, P<.01). Both MACE and MALE were decreased in Group 1. Multivariate analysis found GLP-1 RAs to be significantly associated with decreased risk of persistence of wounds, soft tissue infection, inpatient admission, MACE, and MALE.
CONCLUSIONS: The use of GLP-1 RAs is associated with improved venous ulcer healing. Patients with venous ulcers treated with GLP-1 RAs are also less likely to be admitted to the hospital with wound-associated complications and suffer major adverse cardiovascular events.
