Abstract
<title>Abstract</title> <p> <bold>Introduction:</bold> Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) share overlapping pathophysiological roots in insulin resistance and visceral adiposity. The Metabolic Score for Insulin Resistance (METS-IR), a clamp-validated, non-insulin-based surrogate incorporating fasting glucose, triglycerides, body mass index, and HDL cholesterol, has been associated with incident T2DM across independent cohorts, but reported effect sizes have varied strikingly, and no study has quantitatively pooled these estimates. <bold>Objective:</bold> To systematically synthesize population-based evidence on the association between METS-IR and T2DM risk and, through a translational and mechanistic rationale, evaluate its indirect applicability as a non-invasive risk-stratification surrogate for individuals with obesity-associated metabolic dysfunction-associated steatotic liver disease (MASLD). <bold>Methods:</bold> PubMed/MEDLINE was searched through July 2026 following PRISMA 2020 guidance. Studies reporting a multivariable-adjusted hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) comparing the highest versus lowest METS-IR quartile for T2DM were eligible. Random-effects meta-analysis (DerSimonian-Laird) pooled log-transformed estimates; heterogeneity, leave-one-out sensitivity, funnel-plot, and Newcastle-Ottawa Scale quality assessments were performed. <bold>Results:</bold> Six studies (168,993 participants; Mexico, China, Iran) met eligibility criteria. Individuals in the highest METS-IR quartile had a 3.65-fold higher risk of T2DM than those in the lowest (pooled HR/OR = 3.65, 95% CI: 2.33–5.72, P = 1.75 × 10⁻⁸), with substantial heterogeneity (I² = 95.7%). Leave-one-out analysis confirmed robustness (range: 3.24–4.21); all studies were rated high quality (NOS ≥ 7/9). <bold>Conclusion:</bold> Elevated METS-IR is consistently and robustly associated with markedly increased T2DM risk, supporting its use as an accessible screening tool for risk stratification in obesity-associated MASLD. </p>