Sortilin, a pluripotent peptide hormone, plays a role in glucose and lipid metabolism. A link between sortilin and insulin sensitivity has been implicated. However, the clinical implications of this link remain elusive. Our aims were to investigate whether sortilin levels were altered in subjects with newly diagnosed type 2 diabetes mellitus (nT2DM) compared with subjects with normal glucose tolerance (NGT) and to determine whether a link exist between sortilin levels and metabolic parameters. A total of 150 subjects including 75 nT2DM patients and 75 subjects with NGT who were matched in age, body mass index, and sex were enrolled into this case-control study. The circulating levels of sortilin were measured using enzyme-linked immunosorbent assay. A 2-hour 75-g oral glucose tolerance test was used for diagnosis of T2DM. Metabolic parameters of enrolled subjects were also determined. The circulating levels of sortilin were found to be significantly lower in subjects with nT2DM than in controls (138.44 ± 38.39 vs. 184.93 ± 49.67 pg/mL, P < 0.001). Sortilin levels showed a negative correlation with insulin resistance and unfavorable lipid profiles, while they were positively correlated with high-density lipoprotein cholesterol in subjects with nT2DM. Linear regression analysis showed an independent and inverse link between sortilin and insulin resistance and unfavorable lipid profiles. Moreover, logistic regression analysis revealed that the subjects with the lowest sortilin levels had an increased risk of nT2DM compared with those subjects with the highest sortilin levels. Decreased circulating levels of sortilin were associated with unfavorable metabolic profiles in subjects with nT2DM.