Nicotinamide was shown to prevent damage and to stimulate B cell regeneration in experimental diabetes but in humans results are still controversial. To ascertain if long term nicotinamide treatment can induce and/or prolong remission of the disease, 21 type 1 (insulin-dependent) recently diagnosed subjects entered a controlled study and randomly divided in two groups comparable for age, genetic and immunologic patterns: group 1 (11 subjects) received insulin and nicotinamide (3 g/day for 1 year) and group 2 (10 subjects) insulin alone. Bimonthly insulin requirement and HbA1c, and every 6 months C-peptide response to glucagon were registered for 2 years. No significant difference was observed between the two groups in the monitored parameters, including rates of clinical remission, along this time period. In conclusion nicotinamide, when employed after the clinical onset of the disease, has no additional effect on natural history of newly diagnosed type 1 diabetes mellitus, besides results obtained by insulin alone.