Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Jul 1;12(7):1962.
doi: 10.3390/nu12071962.

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

Ryan Jalleh  1 , Hung Pham  2 , Chinmay S Marathe  1   2 , Tongzhi Wu  1   2 , Madeline D Buttfield  3 , Seva Hatzinikolas  2 , Charles H Malbert  4 , Rachael S Rigda  2 , Kylie Lange  2 , Laurence G Trahair  2 , Christine Feinle-Bisset  2 , Christopher K Rayner  2   5 , Michael Horowitz  1   2 , Karen L Jones  1   2
Affiliations
Randomized Controlled Trial

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

Ryan Jalleh et al. Nutrients. .

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.

Keywords: energy intake; intragastric meal retention; lixisenatide; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

K.L.J. has received research funding from Sanofi and AstraZeneca and drug supplies from Merck Sharp & Dohme. T.W. has received travel support from Novartis and research funding from AstraZeneca. C.K.R. has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly and Company, Novartis, and Sanofi. M.H. has participated in advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly and Company, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. No other potential conflicts of interest relevant to this article are reported.

Figures

Figure 1
Figure 1
Intragastric distribution of gastric content (retention in the total, proximal, and distal stomach regions) at t = 180 min following a 75-g glucose drink radiolabelled with 20 MBq 99mTc-Calcium Phytate in health and type 2 diabetes (T2D) following lixisenatide (10 mcg sc) or placebo (sc). p < 0.001 treatment difference in two-way repeated measures ANOVA. Treatment-by-group interactions all nonsignificant (p > 0.05).
Figure 2
Figure 2
Effect of lixisenatide (10 mcg sc) (open circles) vs. placebo (sc) (black circles) on energy intake (MJ) at a buffet-style meal in healthy participants and patients with T2D p < 0.001 for both (placebo vs. lixisenatide). p < 0.001 treatment difference in two-way repeated measures analysis of variance (ANOVA). Treatment-by-group interaction nonsignificant (p > 0.05).
Figure 3
Figure 3
Relationships between energy intake (MJ) consumed at the buffet-style meal and retention in the distal stomach at 180 min after a drink containing 75 g glucose in healthy participants (black circles) following placebo (r = −0.58, p = 0.03) and lixisenatide (r = −0.16, p =0.58) and patients with T2D (open squares) following placebo (r = −0.31, p = 0.27) and lixisenatide (r = 0.004, p = 0.99).
See this image and copyright information in PMC

References

    1. Meier J.J., Rosenstock J., Hincelin-Méry A., Roy-Duval C., Delfolie A., Coester H.-V., Menge B.A., Forst T., Kapitza C. Contrasting effects of lixisenatide and liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 diabetes on optimized insulin glargine with or without metformin: A randomized, open-label trial. Diabetes Care. 2015;38:1263–1273. doi: 10.2337/dc14-1984. - DOI - PubMed
    1. Halawi H., Khemani D., Eckert D., O′Neill J., Kadouh H., Grothe K., Clark M.M., Burton D.D., Vella A., Acosta A., et al. Effects of liraglutide on weight, satiation, and gastric functions in obesity: A randomised, placebo-controlled pilot trial. Lancet Gastroenterol. Hepatol. 2017;2:890–899. doi: 10.1016/S2468-1253(17)30285-6. - DOI - PubMed
    1. Hjerpsted J.B., Flint A., Brooks A., Axelsen M.B., Kvist T., Blundell J. Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity. Diabetes Obes. Metab. 2018;20:610–619. doi: 10.1111/dom.13120. - DOI - PMC - PubMed
    1. Acosta A., Camilleri M., Burton D., O′Neill J., Eckert D., Carlson P., Zinsmeister A.R. Exenatide in obesity with accelerated gastric emptying: A randomized, pharmacodynamics study. Physiol. Rep. 2015;3:12610. doi: 10.14814/phy2.12610. - DOI - PMC - PubMed
    1. Astrup A., Rossner S., Van Gaal L., Rissanen A., Niskanen L., Al Hakim M., Madsen J., Rasmussen M.F., Lean M.E. Effects of liraglutide in the treatment of obesity: A randomised, double-blind, placebo-controlled study. Lancet. 2009;374:1606–1616. doi: 10.1016/S0140-6736(09)61375-1. - DOI - PubMed

Publication types