Identifying insulin resistance in type 2 diabetes mellitus (T2DM) remains clinically challenging, and the diagnostic role of emerging metabolokines is still being defined. A systematic review and diagnostic test accuracy meta-analysis published in Diabetes Research and Clinical Practice evaluated the performance of fibroblast growth factor-21 (FGF-21) and growth differentiation factor-15 (GDF-15) for identifying insulin resistance.

The analysis searched six databases for studies published between January 2015 and March 2025 and included 15 studies involving 14,832 participants. Diagnostic accuracy was assessed against the triglyceride-glucose (TyG) index, HOMA-C-peptide, and the C-peptide-to-glucose ratio. Across analyses, the TyG index was the most discriminating reference standard for both biomarkers.

Findings

• FGF-21 showed pooled sensitivity of 82.4% and specificity of 78.9%, with an area under the curve (AUC) of 0.88.
• GDF-15 showed slightly higher pooled sensitivity of 85.6% and specificity of 82.1%, with an AUC of 0.91.
• Combined FGF-21 and GDF-15 testing showed the highest diagnostic performance, with pooled sensitivity of 88.9%, specificity of 86.4%, and an AUC of 0.94. 

Pooled findings suggest that FGF-21 and GDF-15, particularly in combination, may serve as adjunctive biomarkers for insulin resistance risk stratification in T2DM.