Exploring the Role of GLP-1 Agents in Managing Diabetic Foot Ulcers: A Narrative and Systematic Review

Abstract

Globally, there are 537 million people with diabetes, with an estimated 19%–344% of these people developing a diabetic foot ulcer, and 10% dying within a year of being diagnosed with a diabetic foot ulcer. Risk factors for developing a diabetic foot ulcer include age, sex, ethnicity, chronically elevated HbA1c, smoking history, cardiovascular disease, end-stage renal disease, and retinopathy. Diabetic foot ulcer recurrence rates are as high as 20%, and they have vast complications, including lower-extremity amputations. More recently, there has been a surge in the use of glucagon-like peptide 1 receptor agonists in managing diabetes and weight loss. The use of glucagon-like peptide 1 receptor agonists in treating diabetic foot ulcers in humans has not been extensively studied, but there are reports of using glucagon-like peptide 1 receptor agonists in other dermatologic diseases with positive outcomes, including androgenetic alopecia and hidradenitis suppurativa. This review aims to explore the potential of using systemic glucagon-like peptide 1 receptor agonists in managing diabetic foot ulcers, describing their effects on modulating wound repair, microvascular function, neuropathic symptoms, apoptosis, weight loss, oxidative stress, and inflammation. Additionally, a systematic review, following PRISMA guidelines, was conducted assessing the rate of diabetic foot complications in patients using glucagon-like peptide 1 receptor agonists when compared to a control group, with the results suggesting their potentially protective role. By managing multiple facets of diabetic foot ulcer pathophysiology, the use of glucagon-like peptide 1 receptor agonists may aid in their management and thus prevent recurrence.