Inhibition of Food Intake in Response to Oral GLP-1 and Peptide YY3-36: a Phase 1 Study

PYY3-36 and GLP-1 are two classical gastrointestinal peptides, which are released into the circulation during meals from L-cells of the distal gut; there is compelling evidence that each participates in the control of appetite regulating individual meal sizes in healthy subjects, but also in patients with obesity or diabetes type II. The regulation of human eating habits is, however, highly complex and our understanding of appetite control is far from complete. In many areas our knowledge is rather rudimentary; little is known, to give an example, about the importance of individual signals and their interactions.

From studies in animals and humans it is known that individual satiety signals can interact: contributions of glucagon and CCK produced functionally synergistic inhibitions of feeding in rats, that is, simultaneous injection of the two peptides inhibited feeding significantly more than the sum of their individual effects. In contrast, we have been unable to show in healthy volunteers any interaction between GLP-1 and CCK33; the simultaneous infusion of CCK33 and GLP-1 resulted in an infra-additive reduction in meal size, which led us to suggest that the two peptides could even interact antagonistically.

To further explore potential interactions between these two well-known satiety signals, we plan to investigate the effects of individual doses of PYY3-36 and GLP-1, and their interaction in the control of food intake and satiety in healthy male subjects.