Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair enzyme poly-ADP-ribose polymerase and prevention of β-cell NAD depletion. We aimed to assess whether high dose nicotinamide prevents or delays clinical onset of diabetes in people with a first-degree family history of type 1 diabetes...We did a randomised double-blind placebo-controlled trial of nicotinamide in 552 relatives with confirmed islet cell antibody (ICA) levels of 20 Juvenile Diabetes Federation (JDF) units or more, and a non-diabetic oral glucose tolerance test. Participants were recruited from 18 European countries, Canada, and the USA, and were randomly allocated oral modified release nicotinamide (1.2 g/m2) or placebo for 5 years...There was no difference in the development of diabetes between the treatment groups...Large-scale controlled trials of interventions designed to prevent the onset of type 1 diabetes are feasible, but nicotinamide was ineffective at the dose we used.