The GLP-1 receptor agonists have changed the trajectory of type 2 diabetes care, and the evidence now suggests their reach extends to the diabetic foot. A nationwide analysis of French health data published in Diabetes Care reported that GLP-1 receptor agonist treatment was associated with reduced mortality in the year following a first diabetic foot ulcer. Recent review work credits the class with plausible mechanisms beyond glucose lowering, spanning effects on peripheral nerves, microcirculation, and inflammation. What the literature has not established is that a systemic GLP-1 receptor agonist closes an established ulcer. A 2025 systematic review in Wound Repair and Regeneration concluded that direct use of GLP-1 agents to treat diabetic foot ulcers remains sparsely studied, and the therapeutic pipeline reflects that gap, with topical candidates for diabetic foot ulcers, including a topically applied cell and gene therapy, still advancing through trials up to phase 3.
For wound care programs, the landscape has therefore shifted without the central problem going away. Patients arriving with chronic wounds will increasingly be on GLP-1 therapy, with better glycemic control than the historical population and, if the proposed vascular mechanisms hold, better perfusion. The ulcer itself still needs a local intervention, and that intervention still needs preclinical evidence from a wound that behaves like a human diabetic wound.
Diabetic wounds do not just heal more slowly, they heal differently. The model therefore has to make the animal diabetic before any wound is made, rather than slowing a healthy wound down. In the MD Biosciences diabetic pig model, diabetes is induced with streptozotocin and verified by blood glucose measurement. Six or more full-thickness excisional wounds are created on the pig back, which allows a candidate, a comparator, and controls to be evaluated in the same animal against the same systemic background. A standard of care comparator is included so that a new dressing or topical agent is measured against what a clinician would otherwise apply.
Pig skin heals similarly to human skin. Pig skin re-epithelializes as human skin does, where rodent wounds close substantially by contraction, and a dressing or gel interacts with pig dermis the way it will interact with human dermis. The wound healing model portfolio covers incisional and excisional wounds in rodents and pigs, burn wounds in domestic pigs and Göttingen minipigs, diabetic and aged comorbidity versions, and study durations from one week for rodent incisional studies to one to three months for minipig burn studies.
A published study run in the MD Biosciences diabetic pig model evaluated a chemokine-scavenging hydrogel wound contact layer built on starPEG-GAG chemistry (Schirmer et al. 2021, Advanced Science). Against the standard of care, the dressing produced greater wound area reduction after 14 days, twice the granulation tissue thickness, and significant reductions in TNFα and IL-8, while pro-regenerative growth factors were preserved in the wound environment, and the treated wounds reached complete closure within 28 days. Alongside closure, the granulation and cytokine data showed the dressing changing the inflammatory state of the wound, which is the mechanism the product was designed around.
That layered endpoint panel is standard in the model. Closure is tracked in-life across the study. Histology quantifies granulation tissue thickness, Herovici staining separates mature from young collagen to show whether repair tissue is maturing, and CD31 immunostaining counts blood vessels to read angiogenesis. The model also supports cytokine and growth factor analysis, including TNFα, IL-8, MCP-1, and VEGF-A.
The first question is the endpoint. A candidate that speeds closure and a candidate that improves the quality of repair are showing different things, and each needs its own endpoints. Faster closure is read from wound area measured across the study. Better repair is read in the histology, in collagen maturity and vascularization, which wound area alone cannot show.
The second question is the comparator. If trial populations continue shifting toward patients on GLP-1 therapy, the control arms of clinical studies may heal against a better systemic background, which would narrow the margin a local therapy has to demonstrate added benefit. That argues for preclinical packages that isolate the local effect cleanly, with within-animal controls, a clinically real comparator, and mechanistic endpoints that survive a smaller effect size on closure. The six-wound diabetic pig design supports that comparison directly, since candidate, comparator, and control sit on the same animal.
Systemic metabolic control is improving the population. It has not replaced wound care, and the programs still working on the ulcer itself need models that reproduce the wound they intend to treat. The model accepts the range of technologies now in the diabetic foot pipeline, from dressings and topical agents to cell and gene therapies; MD Biosciences works with small molecules, biologics, cell-based therapies, AAVs, medical devices and combination products across all administration routes. Study design discussions are welcome at neuro@mdbiosciences.com.
References:
GLP-1 Receptor Agonists Are Associated With Reduced Mortality Following Diabetic Foot Ulcers: A Nationwide Observational Study. Diabetes Care 49(5):730 (2026); French national health data, one-year mortality following a first diabetic foot ulcer.
Gruzmark et al. 2025 (Wound Repair and Regeneration). Exploring the Role of GLP-1 Agents in Managing Diabetic Foot Ulcers: A Narrative and Systematic Review; direct treatment of diabetic foot ulcers with GLP-1 agents identified as sparsely studied.
Effects of Treatment with Glucagon-like Peptide-1 Receptor Analogues on the Diabetic Foot, Biomedicines 14(2):406 (2026); mechanisms spanning peripheral nerves, microcirculation, and inflammation and tissue repair.
Diabetic Foot Ulcers Pipeline Insight (DelveInsight, 2025-2026); topically applied cell and gene therapy candidate in phase 3 development for diabetic foot ulcers, among other pipeline candidates.
Schirmer L, Atallah P, Freudenberg U, Werner C. 2021 (Advanced Science). starPEG-GAG hydrogel wound contact layer with selective chemokine scavenging in the MD Biosciences diabetic pig wound model; greater wound area reduction at 14 days versus standard of care, two-fold granulation tissue thickness, significant TNFα and IL-8 reductions, complete closure within 28 days, pro-regenerative growth factors preserved.