Inhibition of diacylglycerol O-acyltransferase 1 with AZD7687 had intolerable adverse effects when used to treat 62 patients with overweight, report Denison et al. In previous animal studies, inhibition of this enzyme had reduced body weight and adiposity and increased insulin sensitivity. By contrast, in this phase I trial, 1 week of treatment with AZD7687 altered lipid handling and hormone secretion in the gut, but also caused diarrhoea, leading to treatment discontinuation in a number of participants.