Aims: Mutations in the sodium–glucose cotransporter 2 (SGLT2), as well as treatment with SGLT2 inhibitors result in reduced fasting glucose levels, HbA_1c and BMI. We therefore investigated the effects of common genetic variation in SGLT2 on human Type 2 diabetes and related traits. Materials & methods: Four HapMap tagging SNPs covering the common genetic variation in SGLT2 (r₂ > 0.8 and minor allele frequency >0.01) were genotyped for subsequent association studies on BMI, Type 2 diabetes and related metabolic traits in 1013 Sorbs (Germany). An independent cohort from Berlin (n = 2042) was taken for replication. Results: The rs9934336 G-allele was nominally associated with increased 30-min plasma glucose, 120-min insulin concentrations and AUC120min_glucose during oral glucose tolerance test in 907 nondiabetic Sorbs (p < 0.05). In the combined analysis including the Sorbs and the Berlin cohort, rs9934336 was nominally associated with 120-min insulin concentrations (adjusted p < 0.05) in nondiabetic subjects (n = 2590). Conclusion: Our data suggest a role of SGLT2 genetic variation in the regulation of glucose homeostasis and promote pharmacogenomic studies to clarify the efficacy of antidiabetic treatment by SGLT2 inhibitors. Original submitted 2 March 2011; Revision submitted 22 April 2011