The attenuating effect of AZD7687, the selective DGAT1 inhibitor, on postprandial triacylglycerol (TAG) excursion provides proof of mechanism with respect to gut DGAT1 inhibition. Nausea, vomiting and diarrhoea were reported with increasing doses and they limited dose escalation. Lowering of SMM fat content to 45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal symptoms at a given dose of AZD7687.