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Introduction: Low glomerular filtration rate (GFR) is a leading cause of reduced lifespan in type 2 diabetes. Unravelling biomarkers capable to identify high-risk patients can help tackle this burden. We investigated the association between 188 serum metabolites and kidney function in type 2 diabetes and then whether the associated metabolites improve two established clinical models for predicting GFR decline in these patients., Research Design and Methods: Two cohorts comprising 849 individuals with type 2 diabetes (discovery and validation samples) and a follow-up study of 575 patients with estimated GFR (eGFR) decline were analyzed., Results: Ten metabolites were independently associated with low eGFR in the discovery sample, with nine of them being confirmed also in the validation sample (ORs range 1.3-2.4 per 1SD, p values range 1.9×10 -2 -2.5×10 -9 ). Of these, five metabolites were also associated with eGFR decline (ie, tiglylcarnitine, decadienylcarnitine, total dimethylarginine, decenoylcarnitine and kynurenine) (β range -0.11 to -0.19, p values range 4.8×10 -2 to 3.0×10 -3 ). Indeed, tiglylcarnitine and kynurenine, which captured all the information of the other three markers, improved discrimination and reclassification (all p<0.01) of two clinical prediction models of GFR decline in people with diabetes., Conclusions: Further studies are needed to validate our findings in larger cohorts of different clinical, environmental and genetic background., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)