Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA1c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide’s effect on satiety and food intake in humans has not yet been assessed. In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60±9 years, BMI 28.9±4.8 kg/m2) and 15 non-diabetic obese men (age 41±21 years, BMI 34.4±4.5 kg/m2) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 μg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Δ−202±64 kcal, −23±8%, p<0.01) and obese (Δ−170±68 kcal, −16±6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.