The insulinotropic effect of pulsatile compared with continuous intravenous delivery of GLP-1.
Level 2 - randomized trial
Individual randomized double-blind crossover trial
PubMed 26831299 · doi:10.1007/s00125-016-3878-7
What was done
A randomized, double-blind, double-dummy crossover study compared pulsatile versus continuous intravenous administration of GLP-1 in 12 healthy adults aged 18–35 years across three separate test days. Participants received continuous GLP-1 (0.6 pmol/kg/min plus a placebo bolus every 6 min), pulsatile GLP-1 (placebo infusion plus a 3.6 pmol/kg GLP-1 bolus every 6 min), or placebo (infusion and bolus). From 45 to 120 minutes, a hyperglycaemic clamp maintained blood glucose at 9 mmol/l while venous blood glucose, plasma insulin, and plasma glucagon were measured.
What was found
Both continuous and pulsatile GLP-1 infusions increased the dextrose requirement approximately threefold (p < 0.001) and increased insulin secretion approximately ninefold (p < 0.001) compared with placebo. There was no significant difference in effect between continuous and pulsatile delivery modes. Plasma glucagon concentrations decreased during hyperglycaemia, with no difference between treatment days.
Why it matters
Unlike insulin, which has greater glucose-lowering potency when administered in pulses, GLP-1 exerts comparable insulinotropic and metabolic effects whether delivered continuously or in discrete pulses.
Limits
The study included only 12 healthy young individuals, which limits generalizability to patients with type 2 diabetes or obesity. It evaluated only acute, short-duration responses during an intravenous hyperglycaemic clamp rather than physiological oral meal ingestion, and tested only a single pulse frequency.
Cited by
- contradicts Arne Astrup has published multiple human studies demonstrating that GLP-1 does not stimulate insulin secretion or act as an insulin secretagogue in humans.