Karen L Jones1,2,3, Rachael S Rigda1,2, Madeline D M Buttfield1,2, Seva Hatzinikolas1,2, Hung T Pham1,2, Chinmay S Marathe1,2, Tongzhi Wu1,2, Kylie Lange1,2, Laurence G Trahair1,2, Christopher K Rayner1,2,4, Michael Horowitz1,2,3. 1. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. 2. National Health and Medical Research Council (NHMRC), Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia. 3. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 4. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Abstract
AIM: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM). MATERIALS AND METHODS:Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ±SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink. RESULTS:Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001). CONCLUSIONS: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension.
RCT Entities:
AIM: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM). MATERIALS AND METHODS: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink. RESULTS:Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001). CONCLUSIONS: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension.
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Authors: Hung Pham; Iselin S Holen; Liza K Phillips; Seva Hatzinikolas; Lian Q Huynh; Tongzhi Wu; Trygve Hausken; Christopher K Rayner; Michael Horowitz; Karen L Jones Journal: Nutrients Date: 2019-11-05 Impact factor: 5.717
Authors: Ryan Jalleh; Hung Pham; Chinmay S Marathe; Tongzhi Wu; Madeline D Buttfield; Seva Hatzinikolas; Charles H Malbert; Rachael S Rigda; Kylie Lange; Laurence G Trahair; Christine Feinle-Bisset; Christopher K Rayner; Michael Horowitz; Karen L Jones Journal: Nutrients Date: 2020-07-01 Impact factor: 5.717
Authors: Chinmay S Marathe; Hung Pham; Tongzhi Wu; Laurence G Trahair; Rachael S Rigda; Madeline D M Buttfield; Seva Hatzinikolas; Kylie Lange; Christopher K Rayner; Andrea Mari; Michael Horowitz; Karen L Jones Journal: Diabetes Ther Date: 2022-04-22 Impact factor: 3.595
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