Scientific deep-dive
GLP-1 Drugs, Diabetic Foot Ulcers and Blood Flow to the Foot
A randomized trial found liraglutide raised oxygen reaching the skin of the lower limb, with 89% of the drug group improving against 46% of controls. A 125,150-person cohort recorded amputation in 2.34% of semaglutide users against 5.21%.
Among adults who have both type 2 diabetes and peripheral artery disease, six months of liraglutide raised the oxygen reaching the skin of the lower limb. Eighty-nine percent of the drug group hit a 10% improvement in transcutaneous oxygen pressure, against 46% on conventional risk-factor treatment.[1] That is a mechanism, measured with an instrument. Separately, a cohort of 125,150 people with diabetic foot ulcers found amputation recorded in 2.34% of semaglutide users against 5.21% of non-users. That is an association only, and the study’s authors say plainly that causation cannot be inferred.[2]
The randomized half: oxygen reaching the foot
STARDUST enrolled 55 people in Naples with type 2 diabetes, peripheral artery disease and a transcutaneous oxygen pressure between 30 and 49 mm Hg, the band where perfusion is impaired but the limb is not yet critically threatened. They were randomized to 1.8 mg liraglutide or conventional treatment of cardiovascular risk factors for six months.[1]
| Measure | Result | 95% CI |
|---|---|---|
| Transcutaneous oxygen pressure | +11.2 mm Hg | 8.0 to 14.5 (P < .001) |
| Reached a 10% rise in TcPo₂ | 89% vs 46% | RR 1.91 (1.26–2.90) |
| 6-minute walking distance | +25.1 m | 21.8 to 28.3 (P < .001) |
| C-reactive protein | −0.4 mg/dL | −0.7 to −0.07 |
| Urinary albumin-to-creatinine ratio | −119.4 mg/g | −195.0 to −43.8 |
Walking distance is the row a patient would notice most, because it is the one they would feel: twenty-five meters further in six minutes. A far larger semaglutide trial, STRIDE, measured walking distance in 792 people over a year.
The observational half: what happened to the feet
A retrospective cohort drew on the TriNetX US research network across 64 healthcare organizations, comparing 6,329 semaglutide users who had a diabetes-related foot ulcer against 118,821 non-users, matched on age, sex, race and ethnicity. Within one year:[2]
| Outcome | Semaglutide | No semaglutide |
|---|---|---|
| Amputation | 2.34% | 5.21% |
| Chronic non-healing wound | 0.75% | 1.23% |
| Wound healing complications | 0.19% | 0.38% |
| Wound dehiscence | 0.26% | 0.56% |
| Chronic pain | 4.44% | 8.06% |
| Wound care | 2.42% | 4.86% |
Similar patterns held out to five years. But this is a records study, and the direction of the confounding is not obvious: people prescribed semaglutide differ from people who are not, in ways a match on age, sex, race and ethnicity does not capture. The people well enough to be started on a weekly injectable may also be the people who were going to keep their foot.
Causation cannot be inferred due to the study’s observational design.— Lewis et al., Diabetes & Vascular Disease Research, 2025
How to hold the two together
A trial that shows a plausible mechanism and a cohort that shows the outcome you would expect from that mechanism is a stronger position than either on its own. It is still not proof. Nobody has run a randomized trial with amputation as the endpoint, which is the study that would settle it, and until somebody does, the fair description is “consistent and unproven”.
None of this is a reason to start a GLP‑1 to treat a foot ulcer. Neither drug is approved for that, ulcer care is wound care, and the people in both studies were being treated for diabetes. If you have an ulcer, the person to talk to is whoever is dressing it. Our page on GLP-1s and your kidneys covers a diabetes complication where this class does have randomized outcome data, and the methodology explains how we weigh a records study against a trial.
Frequently Asked Questions
References
- 1.Caruso P, Maiorino MI, Longo M, et al. Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: The STARDUST Randomized Clinical Trial JAMA Network Open. 2024. PMID: 38470420.
- 2.Lewis JE, Omenge DK, Patterson AR, et al. The impact of semaglutide on wound healing in diabetes related foot ulcer patients: A TriNetX database study Diabetes & Vascular Disease Research. 2025. PMID: 40080656.
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