Effect of GLP-1RA on circulating SASP levels and wound healing in patients with diabetic foot ulcers: a randomized, placebo-controlled clinical trial

Diabetic foot ulcers (DFUs) is strongly correlated with aging, yet the effects of anti-senescent treatments on DFU wound repair are poorly characterized. We aimed to investigate whether glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of geroprotective agents, promote wound healing in patients with DFUs. In this prospective, randomized placebo-controlled clinical trial, we enrolled 105 eligible participants, who were randomly assigned in a 1:1 ratio to receive either GLP-1RA (liraglutide) or placebo. The primary outcome was wound healing time, and the key secondary outcome encompassed the circulating levels of senescence-associated secretory phenotype (SASP) factors. The mean age of the overall cohort was 73.7 ± 7.9 years, and males accounted for 55.2% of all participants. Patients treated with liraglutide had a significantly shorter wound healing time and a greater reduction in ulcer area at the one-month follow-up. Complete ulcer healing at three months was significantly more prevalent in liraglutide group, while the six-month amputation rate was similar between the two groups. Circulating levels of various SASP components, including interleukins, chemokines, and growth factors, significantly decreased after liraglutide intervention for one month. Liraglutide therapy ameliorates systemic SASP levels and accelerates wound healing in patients with DFUs, providing novel clinical evidence linking geroprotection to wound healing promotion. ChiCTR2500104914 (registered on June 25, 2025).