Acute effects of lixisenatide on intragastric meal distribution: impact on energy intake

International audience; Background and aims: Glucagon-like peptide-1 agonists (GLP-1RAs) induce weight loss in obese patients and, particularly with ‘short-acting’ GLP-1RAs, slow gastric emptying (GE). In healthy subjects, energy intake after a nutrient ‘preload’ is more strongly related to the content of the distal, than the total, stomach. The effect of GLP-1RAs on intragastric meal distribution has not been reported.We evaluated the acute effects of lixisenatide (LIXI) on intragastric distribution of a glucose drink and subsequent energy intake in health and type 2 diabetes (T2DM). Materials and methods: 15 healthy subjects (9M, 6F; age: 67.2 ± 2.3 yr; BMI: 25.4 ± 0.8 kg/m2) and 15 T2DMpatients managed by diet ormetformin (9M, 6F; age: 61.9 ± 2.3 yr; BMI: 30.3 ± 0.7 kg/m2; duration of known diabetes: 5.3 ± 1.2 yr; HbA1c: 6.9 ± 0.2%were studied. All subjects received LIXI (10mcg sc) or placebo (PLAC) on 2 separate days in a randomised, double-blind, crossover fashion 30 min before a 75g glucose drink labelled with 20MBq 99mTc-Calcium Phytate. A lower than usual dose of LIXI was used to maximise tolerability. GE was measured by scintigraphy for 180 min. A region-of-interest was drawn around the total stomach, which was divided into proximal and distal stomach regions. At 180 min each participant was offered a buffet meal and allowed to eat for 30 min to assess subsequent energy intake. Nausea was measured, using a visual analogue questionnaire, prior to receiving study drug, before the drink and at regular intervals during the study. Data are mean ± SEM and PResults: The studies were well tolerated; scores for nausea were uniformly lowwith no difference between PLAC and LIXI in either group. LIXI slowed GE (% total stomach retention at 180 min - health: PLAC 16.0 ± 11.1 vs LIXI 59.5 ± 24.6 ; T2DM: PLAC 14.5 ± 7.5 vs LIXI 54.4 ± 27.5) and increased retention in both the proximal stomach (health: PLAC 6.6 ± 3.5 vs LIXI 40.9 ± 24.6 ; T2DM: PLAC 6.3 ± 4.1 vs LIXI 34.8 ± 24.5) and distal stomach (health: PLAC 9.4 ± 9.1 vs LIXI 18.6 ± 11.1 ; T2DM: PLAC 8.2 ± 4.2 vs LIXI 19.6 ± 10.4); P