Metformin Use, Inflammatory Markers, and Mortality in U.S. Adults with Type 2 Diabetes: A Nationally Representative Cohort Study Using NHANES 2013–2018
Abstract
Metformin has been linked to mortality benefits in type 2 diabetes that may extend beyond glycemic control, but population-level evidence connecting these benefits to inflammation-related pathways remains limited. Using NHANES 2013–2018 data with mortality follow-up through 2019, we examined associations between metformin use and four inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), serum albumin, and high-sensitivity C-reactive protein (hs-CRP), and evaluated their relevance to all-cause and cardiovascular mortality. Among 2,122 adults with self-reported diabetes (60% metformin users; 2,116 with valid mortality follow-up), survey-weighted linear regression adjusted for demographic, socioeconomic, and metabolic covariates showed metformin use was associated with lower NLR (β = - 0.35; 95% CI −0.57, −0.14), lower MLR (β = −0.04; 95% CI −0.06, −0.02), and higher serum albumin (β = +0.11 g/dL; 95% CI 0.06, 0.16); the hs-CRP association was directionally consistent but not significant. Associations for NLR and MLR were essentially unchanged after BMI and HbA1c adjustment, remained robust in an active comparator analysis against sulfonylurea monotherapy, and were consistent across propensity score and overlap weighting sensitivity analyses. Survey-weighted Cox regression linked metformin to lower all-cause (HR 0.64; 95% CI 0.48, 0.86) and cardiovascular mortality (HR 0.49; 95% CI 0.26, 0.94). NLR was independently…
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: 2,122 participants or records.
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