Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution
1
Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide SA 5000, Australia
2
Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide SA 5000, Australia
3
School of Health Sciences, University of South Australia, Adelaide SA 5001, Australia
4
Aniscan, Institut National de la Rechercher Agronomique, 35590 Saint-Gilles, France
5
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide SA 5000, Australia
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(7), 1962; https://doi.org/10.3390/nu12071962
Received: 30 May 2020 / Revised: 24 June 2020 / Accepted: 29 June 2020 / Published: 1 July 2020
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = −0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.