Metformin Is Associated with Reduced Mortality and Systemic Inflammation in HIV: Integrated Evidence from UK Biobank and Real-World Clinical Data
Abstract
Background: Chronic immune activation remains a central driver of morbidity and mortality in human immunodeficiency virus (HIV). Metformin, a widely used antidiabetic agent, has emerging immunometabolic effects that may modulate systemic inflammation and improve outcomes.
Methods: We conducted a two-part analysis combining large-scale proteomic data from the UK Biobank with real-world clinical outcomes from the TriNetX network. In the UK Biobank (n≈500,000), we evaluated associations between metformin use and circulating inflammatory and cytotoxic biomarkers measured by the Olink platform. In TriNetX, we identified HIV-infected patients and compared survival between metformin users and non-users. Propensity score matching (1:1) was performed on demographic and clinical covariates, yielding 1,480 patients per cohort. Survival was assessed using Kaplan–Meier analysis with hazard ratios (HRs) and log-rank testing.
Results: In the UK Biobank, metformin use was associated with significant reductions in key inflammatory mediators, including interleukin-6 and CXCL10, and modulation of cytotoxic signaling pathways. In the matched TriNetX cohort, metformin use was associated with improved survival, with lower mortality compared to non-users (HR 2.19 for non-metformin vs metformin, 95% CI 1.64–2.93; log-rank p<0.0001). Survival curves demonstrated early and sustained separation favoring metformin.
Conclusions: Metformin is associated with reduced systemic inflammation and improved…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 1,480 participants or records.
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