Background Apart from their role in insulin secretion and glucose homeostasis, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) exert a number of extra-pancreatic effects which in the case of GIP remain largely unknown. Design/patients Six obese male patients with diet-controlled type 2 diabetes (T2DM) and six healthy lean male subjects were studied. The protocol included four experiments for each participant that were carried out in randomized order and included: GLP-1 infusion at a rate of 1 pmol/kg/min for 4 h, GIP at a rate of 2 pmol/kg/min, GLP-1 (at 1 pmol/kg/min) with GIP (at 2 pmol/kg/min), and placebo infusion for 4 h. Energy expenditure (EE) was measured throughout with indirect calorimetry and subjects were given a series of visual analogue scales to rate hourly their hunger, fullness, urge to eat and prospective consumption of food. Immediately following termination of the infusions all subjects were offered a free choice buffet lunch and total calorie and macronutrient intake was calculated. Results During GIP infusion there was a trend for healthy subjects to report higher hunger scores and a reduction in EE only when compared with placebo. These parameters remained unchanged in patients with T2DM. Ad libitum energy intake after all four infusions was the same in both groups. Conclusion We report here for the first time that GIP infusion may impact on resting EE and subjective appetite sensations in normal weight healthy subjects and further studies with larger numbers of subjects are required to help define more conclusively the precise role of GIP in energy balance in humans. © 2009 Blackwell Publishing Ltd.