The DPP4 inhibitor vildagliptin may promote diabetic foot ulcer healing by reducing autophagy in patients with diabetes, in addition to its effect on blood sugar levels, Australian research has found.
Coming on the back of data indicating the gliptin improved healing by approximately 35% compared with placebo, the study suggests a novel pathway for its wound healing properties, Queensland investigators say.
Their analysis compared eight patients who received 12 weeks of vildagliptin treatment with nine receiving placebo from a larger clinical trial, with the researchers measuring various molecular markers associated with wound healing in the two groups.
Results showed that the autophagy marker NUP62 was significantly downregulated in the vildagliptin group at week 12 compared to baseline (median expression 0.57 vs. 1.28).
By contrast, there was no significant change observed in the placebo group, the team from the Department of Translational Research in Endocrinology and Diabetes, James Cook University, Twonsville, reported in Diabetology & Metabolic Syndrome (link here).
“Diabetes mellitus may lead to various microangiopathies, including diabetic foot ulcers, often due to undergoing endothelial cell dysfunction,” they wrote.
“Interestingly, DPP-4i(s), including vildagliptin, was found to protect from endothelial cell dysfunction. Perhaps, even more importantly, the protective effect is seen even in a normoglycemic context where vildagliptin attenuates endothelial cell dysfunction in a non-diabetic mouse model.”
“This significant finding suggests that vildagliptin may also affect cellular processes beyond its canonical inhibition of DPP-4.”
On the other hand, both groups showed substantial downregulation of the RIPK3, a necroptosis marker, at week 12 compared to their respective baselines.
While “not completely understood”, this may suggest reduced inflammation within the ulcer, possibly creating a more favourable environment for healing, according to the authors.
All up, eight of the eight patients in the vildagliptin group showed improvement in their ulcer at the close of the four weeks, compared with six of the nine on placebo, the researchers noted.