Diabetic foot ulcers (DFUs) remain one of the leading causes of hospitalization and lower-extremity amputation in people with diabetes. When ulcers fail to respond to standard wound care—debridement, offloading, infection control, and glycemic management—clinicians often look to adjunctive therapies to improve healing and reduce amputation risk. Hyperbaric oxygen therapy (HBOT), which delivers 100% oxygen at increased atmospheric pressure, is one of the most studied of these adjuncts. Over the past decade, several systematic reviews, meta-analyses, and an updated international guideline have refined understanding of where HBOT fits in diabetic foot ulcer management—and where the evidence remains uncertain.
How Hyperbaric Oxygen Therapy Is Thought to Work
HBOT increases the amount of dissolved oxygen in plasma, raising tissue oxygen tension even in poorly perfused wound beds. The proposed mechanisms include enhanced fibroblast proliferation and collagen synthesis, improved leukocyte bactericidal activity, stimulation of angiogenesis through vascular endothelial growth factor pathways, and mobilization of stem/progenitor cells from bone marrow. These effects are the physiological rationale for using HBOT in chronic, hypoxic diabetic wounds, though translating mechanistic benefit into consistent clinical outcomes has proven more complex.
What the Evidence Shows About Wound Healing
The 2015 Cochrane systematic review by Kranke and colleagues, which pooled 12 randomized controlled trials (10 specific to diabetic foot ulcers, 577 participants total), found that HBOT increased the rate of ulcer healing at six weeks, though this short-term benefit did not clearly persist at one-year follow-up. The authors cautioned that trial design and reporting flaws limited confidence in the pooled results.
More recent meta-analyses have reported stronger healing signals. A 2021 systematic review and meta-analysis in Scientific Reports by Sharma and colleagues, analyzing 14 controlled trials (768 participants), found significantly higher complete healing rates with HBOT compared with standard care (OR 0.29, 95% CI 0.14–0.61). A 2022 updated meta-analysis in the Asian Journal of Surgery by Zhang and colleagues, incorporating 20 RCTs (1,263 patients), reported a healing rate roughly 1.9 times higher with HBOT (RR 1.901, 95% CI 1.484–2.435) and a mean reduction in healing time of about 19 days.
What the Evidence Shows About Amputation Risk
Findings on amputation outcomes have been less consistent across reviews. The 2015 Cochrane review found no statistically significant difference in major amputation rates between HBOT and standard care. In contrast, the more recent meta-analyses reached different conclusions: Sharma and colleagues (2021) reported a 40% relative risk reduction in major amputation with HBOT (RR 0.60, 95% CI 0.39–0.92), and Zhang and colleagues (2022) reported a similar reduction (RR 0.518, 95% CI 0.323–0.830). Neither review found a significant effect on minor amputation rates.
The 2023 International Working Group on the Diabetic Foot (IWGDF) guideline update, published in Diabetes/Metabolism Research and Reviews, reviewed 18 RCTs on HBOT and issued a conditional recommendation, graded as low certainty of evidence, to “consider the use of hyperbaric oxygen as an adjunct therapy in neuro-ischemic or ischemic diabetes-related foot ulcers where standard of care alone has failed.” Notably, the guideline working group concluded that while moderate desirable effects were seen for wound healing and ulcer area reduction, “good evidence of benefit in preventing amputation is… lacking”—a more cautious position than some of the individual meta-analyses suggest, reflecting persistent heterogeneity and risk-of-bias concerns across the trial base.
Patient Selection and Practical Considerations
Current guidance directs HBOT toward a specific population: patients with neuro-ischemic or ischemic ulcers that have not responded to optimized standard care, rather than as a first-line or universal adjunct. Adequate vascular perfusion is a prerequisite for HBOT to have any biological effect, since the therapy raises tissue oxygen delivery but cannot substitute for blood flow; transcutaneous oxygen tension (TcPO2) measurement is commonly used to help identify patients more likely to respond and to screen out those with severe, uncorrected ischemia who may need revascularization first.
Access and cost are meaningful practical barriers. The IWGDF working group specifically noted that HBOT requires substantial resources and proximity to a hyperbaric facility, and that limiting its use to patients who happen to have geographic and financial access “may reduce equity” in diabetic foot care. Treatment courses typically involve daily sessions over several weeks, requiring sustained patient commitment.
Adverse effects are generally uncommon but should be part of patient counseling. Reported risks include reversible myopia, barotrauma to the middle ear or sinuses, oxygen toxicity affecting the central nervous system (rarely including seizures), and, in people with insulin-treated diabetes, hypoglycemia during treatment sessions. Contraindications include untreated pneumothorax and certain chemotherapy agents; a history of seizure disorder or pulmonary disease warrants careful pre-treatment evaluation.
Clinical Summary
The evidence base for HBOT in diabetic foot ulcers has grown substantially over the past decade but remains mixed on its most clinically important outcome—amputation prevention. Systematic reviews and meta-analyses generally support a short- to medium-term benefit in wound healing rates, and several report reductions in major amputation, but the most recent international guideline characterizes the certainty of that evidence as low and the effect on amputation as unproven. HBOT is best framed as a conditional, adjunctive option for carefully selected patients with neuro-ischemic or ischemic ulcers that have not responded to standard multidisciplinary wound care, rather than a routine intervention for all diabetic foot ulcers. Ongoing, well-designed, adequately powered trials are needed to clarify which patients derive the greatest benefit and to better define the therapy’s true effect on limb preservation.
References
Kranke P, Bennett MH, Martyn-St James M, Schnabel A, Debus SE, Weibel S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database of Systematic Reviews. 2015;(6):CD004123.
Sharma R, Sharma SK, Mudgal SK, Jelly P, Thakur K. Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials. Scientific Reports. 2021;11:2189.
Zhang Z, Zhang W, Xu Y, Liu D. Efficacy of hyperbaric oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis. Asian Journal of Surgery. 2022;45(1):68–78.
Chen P, Vilorio NC, Dhatariya K, et al. Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes/Metabolism Research and Reviews. 2024;40(3):e3644.
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