TL;DR: Multiple systematic reviews and meta-analyses published in 2024–2025 confirm that hyperbaric oxygen therapy (HBOT) significantly improves diabetic foot ulcer (DFU) healing rates and reduces the risk of major amputation. Across studies encompassing thousands of patients and dozens of randomised controlled trials, HBOT consistently demonstrates clinical benefit as an adjunctive therapy for non-healing diabetic wounds.
Hyperbaric oxygen therapy (HBOT) is a proven adjunctive treatment for non-healing diabetic wounds, working by delivering oxygen to tissue that has been compromised by poor circulation. Hyperbaric oxygen therapy (HBOT) is a non-invasive treatment that delivers 100% oxygen at pressures greater than atmospheric pressure, enhancing tissue oxygenation to promote wound healing. For researchers investigating advanced wound care interventions, the 2024–2025 evidence base offers a substantial body of systematic reviews and network meta-analyses that clarify where HBOT sits in the hierarchy of diabetic foot ulcer management. This research summary synthesises the most recent high-quality evidence on HBOT for diabetic wound healing.
Estimated reading time: 7 minutes
Why Is Diabetic Wound Healing a Critical Research Priority?
Diabetic foot ulcers affect approximately 15–25% of individuals with diabetes mellitus at some point during their lifetime. These chronic wounds carry substantial morbidity, with non-healing DFUs representing the leading cause of non-traumatic lower-extremity amputation worldwide. In Canada, diabetes affects over 3.7 million people, and the economic burden of DFU-related complications – including hospitalisation, amputation, rehabilitation, and long-term care – places significant strain on provincial health systems.
Standard wound care alone fails to achieve healing in a substantial proportion of DFU patients, driving ongoing research into adjunctive therapies. HBOT has been used for decades as a treatment for non-healing wounds and other approved indications, but the quality and scope of supporting evidence has expanded considerably in recent years. Several large-scale evidence syntheses published in 2024 and 2025 now provide researchers with a more comprehensive picture of HBOT’s clinical effectiveness.
What Does the Latest Systematic Review Evidence Show?
A 2025 systematic review published in Cureus by Damineni et al. evaluated the primary clinical evidence for HBOT in DFU management. The review analysed six studies encompassing 391 patients and assessed outcomes including ulcer healing rates, ulcer size reduction, and major amputation rates using both the Cochrane Risk of Bias (RoB 2.0) tool for RCTs and the ROBINS-I tool for observational studies (DOI: 10.7759/cureus.78655).
The majority of included studies demonstrated that HBOT led to reduced major amputation rates, improved ulcer healing rates, and decreased ulcer size and depth compared to standard care. However, the authors noted one study that found no significant differences between groups, and they highlighted methodological limitations including selection bias and insufficient blinding across some included studies. The review concluded that while evidence supports HBOT as a valuable adjunctive therapy for DFUs, future high-quality RCTs with stringent blinding and standardised protocols are needed to strengthen the evidence base.
How Does HBOT Compare to Other Advanced DFU Interventions?
One of the most comprehensive evidence syntheses on this topic is the 2025 network meta-analysis by Hu et al., published in PeerJ. This analysis included 99 randomised controlled trials involving 7,356 patients and compared the efficacy of 12 different interventions for DFU treatment, including HBOT, stem cells, platelet-rich plasma (PRP), negative pressure wound therapy (NPWT), low-level laser therapy (LLLT), extracorporeal shockwave therapy (ESWT), and others (DOI: 10.7717/peerj.19809).
Key findings relevant to HBOT researchers:
- Amputation reduction: HBOT significantly lowered amputation risk compared to standard of care (OR = 0.35; 95% CI [0.16–0.78])
- Healing rate: HBOT improved ulcer healing rates, though stem cell therapy and amniotic membrane therapy ranked highest in SUCRA rankings for this outcome
- Comparative positioning: While HBOT demonstrated clear benefits over standard care, newer biological therapies (stem cells, amniotic membrane) showed superior efficacy for certain endpoints
This positions HBOT as an established, evidence-based adjunctive therapy with particular strength in amputation prevention, while highlighting emerging biological approaches that warrant further comparative study.
What Do Meta-Analyses Reveal About Amputation Risk Reduction?
The reduction in major amputation risk is consistently identified as one of HBOT’s most clinically significant outcomes. The 2024 meta-analysis by Monami et al. in Acta Diabetologica – designed to inform Italian clinical guidelines – analysed 51 RCTs across five adjunctive therapy categories and found that HBOT significantly reduced major amputation risk with an odds ratio of 0.28 (95% CI [0.10–0.79]; p = 0.02) (DOI: 10.1007/s00592-024-02426-7).
This finding is particularly noteworthy because only two of the five adjunctive therapies assessed – HBOT and platelet-rich plasma/fibrin – demonstrated statistically significant amputation risk reduction. The quality of evidence for the healing endpoint was rated as “high” for HBOT. However, the meta-analysis also noted that HBOT was associated with a higher rate of serious adverse events compared to standard care, underscoring the importance of careful patient selection and clinical monitoring.
A separate 2025 meta-analysis by Zhang et al. in the International Journal of Burns and Trauma corroborated these findings, reporting that systemic HBOT demonstrated a substantial reduction in amputation rates (OR = 0.08; 95% CI [−0.11–0.28]) compared to controls (DOI: 10.62347/WVEM7973).
Comparative Amputation Risk Reduction Across Studies
| Study | Year | Design | Amputation OR (95% CI) | Significance |
|---|---|---|---|---|
| Monami et al. | 2024 | Meta-analysis (8 HBOT RCTs) | 0.28 (0.10–0.79) | p = 0.02 |
| Hu et al. | 2025 | Network meta-analysis (99 RCTs) | 0.35 (0.16–0.78) | Significant |
| Zhang et al. | 2025 | Meta-analysis (10 RCTs) | 0.08 (−0.11–0.28) | Favours HBOT |
What Does the Latest RCT Data Show?
A 2025 randomised controlled trial by Nguyen et al. at the Institute of Maritime Medicine provides granular clinical data on HBOT outcomes. The study enrolled 94 patients with DFUs and compared HBOT combined with standard care (antibiotics, wound care, and disease management) against standard care alone (DOI: 10.5603/imh.102276).
Results demonstrated several clinically meaningful differences:
- Infection control: The HBOT group showed significantly better infection status (p < 0.001)
- Granulation tissue: Greater granulation tissue growth in the HBOT group (p < 0.001)
- Ulcer dimensions: Significant reduction in ulcer depth and diameter (p < 0.05)
- Healing time: 10.1 ± 4.6 days versus 15.1 ± 7.8 days in the control group
- Amputation rate: 4.6% versus 11.7% in the control group
These findings align with the proposed mechanisms of HBOT in wound healing: enhanced angiogenesis, increased collagen synthesis, anti-inflammatory effects, and improved antimicrobial activity through reactive oxygen species generation.
What Are the Key Limitations and Research Gaps?
Despite the overall positive evidence trajectory, researchers should note several important limitations identified across the 2024–2025 evidence base:
- Heterogeneity: Substantial heterogeneity exists across studies in terms of HBOT protocols (pressure levels, session duration, total number of treatments), wound classification systems, and follow-up periods
- Blinding challenges: The nature of HBOT makes double-blinding difficult, introducing potential performance bias
- Sample sizes: Many individual RCTs remain relatively small, limiting statistical power for subgroup analyses
- Standardisation: No universally adopted protocol exists for HBOT in DFU management, complicating cross-study comparisons
- Long-term outcomes: Most studies report short-to-medium-term outcomes; long-term recurrence rates and durability of healing remain understudied
- Cost-effectiveness: Few studies incorporate formal health economic analyses, which are essential for informing clinical guidelines and coverage decisions
Canadian researchers are well positioned to address several of these gaps. The Canadian Undersea and Hyperbaric Medical Association (CUHMA) has advocated for standardised treatment protocols, and Canada’s universal healthcare framework provides an opportunity for large-scale, multi-centre pragmatic trials that could generate the real-world evidence needed to refine clinical guidelines.
What Does This Mean for Clinical Practice and Future Research?
The convergence of evidence from multiple systematic reviews and meta-analyses strengthens the case for HBOT as a clinically meaningful adjunctive therapy for diabetic foot ulcers. The most robust evidence supports HBOT’s role in reducing major amputation risk – a finding consistently replicated across independent research groups using different analytical approaches.
For researchers, several avenues warrant further investigation:
- Protocol optimisation: Determining optimal pressure, duration, and frequency of HBOT sessions for DFU
- Patient stratification: Identifying which DFU patients benefit most from HBOT (e.g., by Wagner grade, perfusion status, or comorbidity profile)
- Combination therapies: Evaluating HBOT in combination with newer biological therapies such as stem cells or growth factors
- Health economics: Conducting cost-effectiveness analyses within Canadian provincial health systems
- Mechanistic studies: Further elucidating the molecular pathways through which HBOT promotes diabetic wound healing
Canada Hyperbarics maintains a comprehensive research database with thousands of peer-reviewed studies on hyperbaric oxygen therapy. Researchers can explore the full evidence base across all UHMS-approved and investigational indications. For information about accessing HBOT at accredited facilities across Canada, visit our clinic directory.
Frequently Asked Questions
Is HBOT an approved treatment for diabetic foot ulcers in Canada?
Yes. Non-healing wounds, including diabetic foot ulcers, are among the UHMS-approved indications for hyperbaric oxygen therapy. In Canada, HBOT for DFUs is available at accredited hospital-based and private hyperbaric facilities, with provincial coverage varying by jurisdiction.
How many HBOT sessions are typically required for diabetic wound healing?
Treatment protocols vary, but most studies report protocols of 20–40 sessions at 2.0–2.5 atmospheres absolute (ATA) for 60–90 minutes per session. The optimal protocol remains an active area of research, and treatment duration should be guided by clinical response.
Does HBOT replace standard wound care for diabetic foot ulcers?
No. HBOT is used as an adjunctive therapy alongside standard wound care, which includes debridement, offloading, infection management, glycaemic control, and vascular assessment. The evidence reviewed here evaluates HBOT combined with standard care versus standard care alone.
What is the strongest evidence for HBOT in DFU management?
The most consistent finding across 2024–2025 systematic reviews is the reduction in major amputation risk, with odds ratios ranging from 0.08 to 0.35 across multiple independent meta-analyses. Evidence for improved healing rates is also strong but shows more variability across studies.
Are there risks associated with HBOT for diabetic patients?
HBOT is generally well tolerated, but potential adverse effects include barotrauma (ear, sinus), transient myopia, and, rarely, oxygen toxicity seizures. The 2024 Monami et al. meta-analysis noted a higher rate of serious adverse events in HBOT groups compared to controls, highlighting the need for appropriate patient screening and clinical monitoring. Refer to the Canada Hyperbarics FAQ for detailed safety information.
How does HBOT compare to newer biological therapies for DFU?
The 2025 Hu et al. network meta-analysis found that stem cell therapy and amniotic membrane therapy ranked higher than HBOT for ulcer healing rate, while HBOT demonstrated particular strength in amputation prevention. These findings suggest potential for combination approaches, which warrant further study.
Is HBOT for diabetic wounds covered by provincial health insurance in Canada?
Coverage varies by province. In Ontario, OHIP covers HBOT for approved indications at both hospital-based and eligible private clinics. Other provinces such as British Columbia (MSP), Alberta (AHCIP), and Quebec (RAMQ) provide coverage primarily through hospital-based programmes. Private insurance may also cover HBOT depending on the plan.
Where can researchers access the full evidence base on HBOT?
Canada Hyperbarics maintains a searchable research database with thousands of peer-reviewed studies across all HBOT indications, including diabetic wound healing. The database supports multi-filter search by condition, study type, and publication year.
This content is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider for clinical decision-making regarding hyperbaric oxygen therapy.