Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing with an epidemic growth rate. Animal studies with taurine supplementation have shown increased insulin secretion and action, suggesting that taurine supplementation may have a potential to prevent T2DM. Objective: To assess the effect of taurine treatment on insulin secretion and action, and on plasma lipid levels in overweight men with a positive history of T2DM. Design: 20 nondiabetic subjects were included in a double-blinded, randomized, crossover study, receiving a daily supplementation of 1.5 g taurine or placebo for two periods of 8 weeks. The subjects were overweight first-degree relatives of T2DM patients. An intravenous glucose tolerance test (IVGTT) was used to measure first-phase insulin secretory response, and a euglycemic hyperinsulinemic clamp was used to determine peripheral insulin action. Results: Mean plasma taurine concentration was 3977 (s.d.) mmol/l after placebo and 131762 mmol/l after taurine intervention (Po0.0001). There was no significant difference after taurine intervention compared to placebo in incremental insulin response (Ins incr. ) neither during the IVGTT, nor in insulin-stimulated glucose disposal during the clamp. Insulin secretion, adjusted for insulin sensitivity, was also unchanged. There was no significant effect of taurine supplementation on blood lipid levels as well. Conclusion: Daily supplementation with 1.5 g taurine for 8 weeks had no effect on insulin secretion or sensitivity, or on blood lipid levels. These findings in persons with an increased risk of T2DM are in contrast to those from animal studies, and do not support the assumption that dietary supplementation with taurine can be used to prevent the development of T2DM.