Combined FGF-21 and GDF-15 show high diagnostic accuracy for insulin resistance in type 2 diabetesNew Biomarkers May Help Identify Insulin Resistance in Type 2 Diabetes

Fibroblast growth factor-21 (FGF-21) and growth differentiation factor-15 (GDF-15) are metabolokines associated with insulin resistance in type 2 diabetes, but their pooled diagnostic performance has not been systematically established. We conducted a PRISMA-DTA-compliant systematic review and bivariate diagnostic test accuracy meta-analysis to evaluate the accuracy of FGF-21 and GDF-15, individually and in combination, for predicting insulin resistance using the triglyceride-glucose (TyG) index, HOMA-C-peptide, and C-peptide-to-glucose ratio as reference standards. Six databases were searched from January 2015 to March 2025. Fifteen studies involving 14,832 participants were included. Against TyG, FGF-21 showed pooled sensitivity of 82.4% and specificity of 78.9% (AUC 0.88), while GDF-15 demonstrated slightly higher sensitivity of 85.6% and specificity of 82.1% (AUC 0.91). Combined FGF-21 and GDF-15 testing achieved the best overall performance, with sensitivity of 88.9%, specificity of 86.4%, and AUC of 0.94. TyG was the most discriminating reference standard across both biomarkers. These findings support the potential utility of FGF-21 and GDF-15, particularly in combination, as adjunctive laboratory biomarkers for insulin resistance risk stratification in type 2 diabetes.