Glucagon-like peptide-1: a potent regulator of food intake in humans

Abstract

Background/aims: Studies in animals suggest a physiological role for glucagon-like peptide-1-(7-36)-amide (GLP-1) in regulating satiety. The role of GLP-1 in regulating food intake in man has, however, not been investigated. Subjects-Sixteen healthy male subjects were examined in a double blind placebo controlled fashion.

Methods: The effect of graded intravenous doses (0, 0.375, 0.75, and 1.5 pmol/kg/min) of synthetic human GLP-1 on food intake and feelings of hunger and satiety was tested in healthy volunteers.

Results: Graded GLP-1 infusions resulted in a dose dependent reduction in food intake (maximal inhibition 35%, p<0.001 v control) and a similar reduction in calorie intake (32%; p<0.001). Fluid ingestion was also reduced by GLP-1 (18% reduction, p<0.01). No overt side effects were produced by GLP-1, but subjects experienced less hunger and early fullness in the period before a meal during GLP-1 infusion at the highest dose (p<0.05).

Conclusions: Intravenous infusions of GLP-1 decrease spontaneous food intake even at physiological plasma concentrations, implying an important role for GLP-1 in the regulation of the early satiety response in humans.

Figure 1

Daily time course of procedures.

Figure 2

Subjective sensations of hunger (A) and fullness (B) experienced by healthy male subjects before and after food intake during intravenous infusion of 5% glucose (placebo) or one dose (0.375, 0.75, or 1.5 pmol/kg/min) of human glucagon-like peptide-1. Results are expressed as mean and SEM (n = 16). *p<0.05, **p<0.01 v control.

Figure 3

Immunoreactive glucagon-like peptide-1 (IR-GLP-1) measured in the plasma (pmol/l) in response to graded doses of intravenous GLP-1 or placebo in the preprandial period. Data are expressed as mean and SEM.

Figure 4

Insulinogenic index (insulin/glucose) and plasma cholecystokinin (CCK) levels (pmol/l) in response to graded doses of glucagon-like peptide-1 (GLP-1) or placebo in the premeal period. Data are expressed as mean and SEM.

Figure 5

Leptin concentrations(ng/ml) measured in plasma in response to graded doses of intravenous glucagon-like peptide-1 (GLP-1) or placebo. Data are expressed as mean and SEM.