No effect of glucagon-like peptide-1 on short-term satiety and energy intake in man

Abstract

Centrally administered glucagon-like peptide-1 (GLP-1) inhibits feeding in fasted rats, but its role in human satiety has been largely unexplored. The present study investigated the effect of peripheral GLP-1 infusion on gastric emptying and satiety in man. Ten non-obese male subjects were infused in a randomized single-blind within-subject crossover study using saline infusion as control. They received either a GLP-1 infusion (1·2 pmol/kg per min) or a saline infusion for 1 h, at 18.00 hours. At 20 min after starting the infusion the gastric emptying of a 400 ml water load was measured. Subjects completed behavioural self-rating scales to assess hunger and satiety. After 40 min subjects were given a buffet meal ad libitum and their food intake was recorded. GLP-1 infusion raised circulating GLP-1 concentrations to approximately twice those seen following a meal. It did not affect circulating insulin levels but caused a small fall in glucose levels. Gastric emptying of the water load was significantly delayed by the GLP-1 infusion. Energy intake from the buffet was unaffected by GLP-1 infusion. Self-assessment of hunger and satiety was similarly unaffected by the infusion before the buffet meal, although subjects tended to be less hungry after the buffet meal following GLP-1 infusion (P < 0·09). GLP-1 infusion delayed gastric emptying but had a minimal effect on food intake and satiety. This study casts doubts on whether GLP-1 is a major satiety factor in man, although a raised circulating plasma glucose level, as would normally occur postprandially, might be necessary for GLP-1 to increase satiety.

Carbohydrate and Satiety

“…78 Comparable observations were made by Flint et al 77 In studies of both obese 80,81 and type 2 diabetic 82,83 patients, a suppressive effect of intravenous GLP-1 on food intake and perceptions of appetite was also evident. By contrast, in two studies, one in healthy 84 and one in obese 23 subjects, GLP-1 had no effect on food intake. Whereas plasma GLP-1 levels rise within 10 to 20 minutes of meal ingestion, peak levels usually occur no earlier than at 30 minutes.…”

Effects of peripheral administration of synthetic human glucose‐dependent insulinotropic peptide (GIP) on energy expenditure and subjective appetite sensations in healthy normal weight subjects and obese patients with type 2 diabetes

“…The effects of GLP‐1 as a potential regulator of appetite and food intake have been well‐explored 20–29 . The lack of an inhibitory effect of GIP on gastric emptying, 30 in marked contrast to GLP‐1, cannot fully explain its effects on appetite.…”

Is the GLP-1 system a viable therapeutic target for weight reduction?

“…In this analysis, the GLP-1 infusion rate was the only independent predictor of reduced energy intake. However, the negative effects of GLP-1 on satiety and food intake have not been universally observed [18, 19]. Proof of concept for the feasibility of using native GLP-1 for therapeutic purpose was obtained from a 6-week study of patients with type 2 diabetes [20].…”