Network meta-analysis of metformin, probiotics, krill oil, celecoxib, and glucosamine/chondroitin in the treatment of knee osteoarthritis
Abstract
Purpose: Knee osteoarthritis (KOA) creates a substantial global socioeconomic burden. Celecoxib remains a standard pharmacological treatment, but its long-term safety profile raises concerns. Several adjuvant therapies-probiotics, metformin, krill oil, and glucosamine/chondroitin (CS+GH)-have produced encouraging results in individual trials; however, direct head-to-head comparisons are absent. This network meta-analysis (NMA) compares the efficacy and safety of these five interventions to inform individualized treatment decisions in clinical practice.
Methods: RCTs published from database inception through February 2026 were retrieved from PubMed, Web of Science, Embase, and the Cochrane Library. A random-effects NMA was conducted using Stata 18.0 and R (MetaInsight). Continuous outcomes were synthesized as mean differences (MD) and dichotomous safety endpoints as risk ratios (RR). Interventions were ranked by surface under the cumulative ranking curve (SUCRA), and evidence quality was assessed using the GRADE framework.
Results: Twenty-three RCTs met the inclusion criteria. No significant network inconsistency (P > 0.05) or publication bias was detected. For analgesic efficacy, celecoxib ranked highest on VAS pain improvement (MD = -0.48, 95% CI -0.78 to -0.17, SUCRA = 0.93) and WOMAC total scores (SUCRA = 0.912), followed by CS+GH (0.756). Probiotics (0.66) and metformin (0.63) showed potential efficacy, but the final network certainty for most of these auxiliary…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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