Aim: This study assessed the efficacy of long‐term l‐arginine (l‐arg) therapy in preventing or delaying type 2 diabetes mellitus.
Methods: A mono‐centre, randomized, double‐blind, parallel‐group, placebo‐controlled, phase III trial (l‐arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l‐Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12‐month extended follow‐up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study.
Results: After 18 months, l‐arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58–1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51–4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l‐arg (HR, 3.21; 95% CI, 1.87–5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l‐arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24–0.75, p < 0.05). During both periods, l‐arg significantly improved insulin sensitivity and β‐cell function.
Conclusion: Among persons with IGT and MS, the supplementation of l‐arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.