Triglyceride-Glucose Index and Mortality Risk in the General Population: A Systematic Review and Meta-analysis of Prospective Studies

Introduction: Insulin resistance (IR) is a major determinant of cardiovascular disease and mortality, yet its direct measurement is limited by the need for insulin assays. The triglyceride–glucose (TyG) index has emerged as a simple and inexpensive surrogate marker of IR, but its prognostic relevance for mortality remains uncertain due to the heterogeneity of available studies. Aim: This study aimed to: (i) evaluate the predictive value of the TyG index for all-cause and cardiovascular mortality risk in the general population; (ii) assess the shape and magnitude of the dose–response relationship; and (iii) identify the most appropriate threshold for mortality risk prediction. Methods: A systematic review and dose–response meta-analysis was conducted, including prospective cohort studies that assessed baseline TyG and subsequent mortality. Random-effects models were used to pool hazard ratios, and restricted cubic splines were applied to examine potential non-linearity in the dose–response relationship. Results: Twelve studies comprising 14 independent cohorts (≈10.8 million participants) were included. Each one-unit increase in TyG was associated with a 14% higher risk of all-cause mortality and a 16% higher risk of cardiovascular mortality starting from 6.9 units (or 3.79 units in the alternative scale). Associations were linear and consistent across sensitivity analyses. There was a significant heterogeneity among studies, but no evidence of publication bias. Conclusion: The TyG index independently and linearly predicts all-cause and cardiovascular mortality, supporting its potential role as a clinically useful, low-cost marker for early cardio-metabolic risk stratification in population-based settings.