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 < 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.
Highlights
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs)—both ‘short’ and ‘long’ acting—induce moderate weight loss in obese subjects with or without type 2 diabetes (T2D) [1,2,3,4,5]
Our study evaluated the acute effects of the ‘short-acting’ GLP-1RA lixisenatide on energy intake at
Doses of lixisenatide less than 20 mcg are, frequently used in practice, in combination with insulin glargine, which has been shown frequently used in practice, in combination with insulin glargine, which has tohowever, be well tolerated and associated with weight loss [23,24]
Summary
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs)—both ‘short’ and ‘long’ acting—induce moderate weight loss in obese subjects with or without type 2 diabetes (T2D) [1,2,3,4,5]. The mechanisms underlying this weight loss are poorly defined. ‘Long-acting’ GLP-1RAs, which are used widely in the management of obesity, probably have a lesser effect on gastric emptying, so that both preprandial and postprandial glucose lowering may be attributable primarily to their insulinotropic and glucagonostatic properties [9]; it is clear that long-acting GLP-1RAs do slow gastric emptying [10]. Larger molecule GLP-1RAs that are unable to cross the blood–brain barrier appear to act via secondary signals from the vagus nerve [14], while smaller molecule GLP-1RAs, including lixisenatide, pass through the blood–brain barrier directly [15]
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