Preclinical and limited clinical evidence for metformin in ulcerative colitis: a systematic review and meta-analysis
Abstract
This study systematically evaluated the preclinical efficacy and limited clinical evidence of metformin as a potential repurposed therapy for ulcerative colitis (UC) and explored candidate mechanisms using multi-omics and in silico analyses. Controlled animal studies were quantitatively synthesized using random-effects meta-analysis. Human randomized controlled trials (RCTs) were summarized narratively because of the limited number of trials and heterogeneity in clinical endpoints. Exploratory 3D response surface modeling, network pharmacology, molecular docking, molecular dynamics (MD) simulations, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) were integrated to prioritize potential dose-duration patterns and candidate mechanistic pathways. Eight preclinical animal studies and three human RCTs involving 232 patients were included. In animal models, metformin was associated with improvements in core colitis-related outcomes, including disease activity index, colon length, body weight change, and histopathological score. However, the magnitude of the pooled standardized mean differences should be interpreted cautiously because of small sample sizes, methodological heterogeneity, and potential small-study effects. Exploratory response surface modeling suggested a potential association between low-dose, long-duration regimens and larger preclinical effect estimates, but this pattern should not be interpreted as a validated dosing recommendation.…
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: 232 participants or records.
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