Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution

Abstract

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 p p 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.

Keywords

• lixisenatide
• intragastric meal retention
• energy intake
• type 2 diabetes