Topical oxygen therapy for diabetic foot ulcers: evidence and limits

Topical oxygen therapy may help some diabetes-related foot ulcers heal when added to appropriate wound care. It is an option for assessment by a diabetic-foot team, not a replacement for pressure relief, infection treatment or restoration of blood flow. The 2023 IWGDF wound-healing guideline gives a conditional recommendation, with low-certainty evidence, for considering it when standard care has failed and resources are available.

What does topical oxygen treatment involve?

Topical systems deliver oxygen at the wound, using approaches such as continuous delivery beneath a dressing or cyclical treatment within a local chamber. These devices and their protocols differ. Evidence from one system should not automatically be applied to another product, and topical treatment should not be confused with whole-body hyperbaric oxygen treatment.

What did the randomized trials find?

A 2021 open-label trial of continuous topical oxygen randomized 145 people to standard care with or without the treatment. At 12 weeks, complete healing occurred in 36 of 81 participants receiving oxygen (44.4%) and 18 of 64 controls (28.1%). Standard care included wound treatment and offloading. Because participants and clinicians knew the allocation, the trial was not blinded. Its result applies to the studied patients and treatment protocol, not every diabetic foot wound. The paper discloses funding and sponsorship by Inotec AMD.

The TWO2 trial used a randomized, double-blind, sham-controlled design. At its first planned analysis of 73 participants, 12-week closure was 41.7% with active cyclical oxygen and 13.5% with sham treatment. It stopped after meeting its prespecified sequential stopping rule. The result is encouraging, but the small sample and early stopping limit certainty about the size of benefit. The trial was sponsored by AOTI. These two trials tested different delivery approaches; their percentages are not a head-to-head product comparison.

What did the 2026 evidence review add?

A 2026 systematic review pooled three trials involving 325 people with 12-week closure results. Its primary analysis reported a relative risk of 1.53 (95% confidence interval 1.14 to 2.05). This is a relative comparison, not a 53-percentage-point improvement. A more conservative sensitivity analysis produced wider uncertainty, reflecting the small number of studies. A published correction accompanies this review; readers assessing the paper should consult it alongside the original.

These results support discussing topical oxygen as an adjunct, while leaving questions about which device suits which patient, longer-term outcomes and value for money. The IWGDF recommendation does not establish an amputation-prevention benefit or identify one delivery device as best.

What evidence comes from Singapore?

The OTONAL study at Singapore General Hospital followed 20 patients receiving continuous topical oxygen plus standard care. Fourteen achieved more than 75% wound closure by 12 weeks. This is not the same as 14 completely healed wounds. Eighteen patients had also undergone angioplasty to improve blood flow.

OTONAL was a small, single-arm study without a control group. It shows experience in a local clinical setting, but cannot separate the effect of oxygen from vascular treatment and other care. The paper reports manufacturer device support, a distributor grant and an author's relevant travel and speaking support. Its findings are not proof that any particular oxygen product works for every patient in Singapore.

How should you discuss this with your wound-care team?

Ask which device is being proposed, whether its studies match your ulcer and circulation status, what usual care will continue, and how progress will be measured. Request the full cost of treatment and follow-up; this article cannot verify an individual clinic's charges or product availability.

Oxygen treatment is also not a substitute for treating infection. The IWGDF/IDSA infection guideline advises against using topical or hyperbaric oxygen for the sole purpose of treating a diabetic foot infection.

When should you seek urgent care?

A new diabetic foot ulcer needs prompt clinical assessment. An ulcer with fever, suspected deep infection, poor blood supply or gangrene needs immediate care; do not wait to arrange oxygen treatment. NICE guidance sets out urgent referral pathways for these problems. Use the local emergency or diabetic-foot service advised by your treating team.

This article covers clinical evidence for topical oxygen devices. It does not establish efficacy for haemoglobin sprays such as Granulox, which require their own product-specific evidence and instructions.