Adjunctive therapies added to standard of care for diabetic foot ulcers: a systematic review and network meta-analysis with pairwise comparisons
Abstract
Background: Diabetic foot ulcers (DFUs) remain one of the most disabling and costly complications of diabetes. Although standard of care (SOC) is the foundation of DFU management, many ulcers fail to heal adequately, prompting increasing use of adjunctive therapies. However, the comparative effectiveness of different adjunctive strategies remains uncertain.
Objective: To evaluate and compare the efficacy and safety of adjunctive therapies added to SOC for patients with DFUs using systematic review, pairwise meta-analysis, and network meta-analysis.
Methods: PubMed, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, WHO ICTRP, and ChiCTR were searched from inception to February 18, 2026. Randomized controlled trials evaluating adjunctive therapies plus SOC for DFUs were included. Interventions were classified into eight clinically interpretable categories: oxygen-based therapies, device-based and physical wound therapies, growth factor and blood-derived therapies, placental and perinatal tissue-derived products, acellular matrix/skin substitute/scaffold products, cell-based and adipose-derived therapies, topical pharmacologic and bioactive agents, and nanotechnology-based, natural product, and bioactive dressing therapies. Outcomes included ulcer area reduction, complete healing, time to healing, adverse events, and amputation.
Results: Eighty-four randomized controlled trials involving 7,232 participants were included. Compared with SOC alone, several adjunctive therapies…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,232 participants or records.
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