Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Acute effects of lixisenatide on gastric emptying, glycaemic and blood pressure responses to oral glucose in health and type 2 diabetes (#112)

Karen L Jones 1 , Rachael S Rigda 1 , Madeline D Buttfield 2 , Seva Hatzinikolas 1 , Hung Pham 1 , Chinmay S Marathe 1 , Tongzhi Wu 1 , Kylie Lange 1 , Laurence G Trahair 1 , Chris K Rayner 1 , Michael Horowitz 1
  1. The University of Adelaide, Adelaide, SA, Australia
  2. School of Health Sciences, University of South Australia, Adelaide, SA, Australia

Introduction: Postprandial hypotension (PPH), a fall in systolic blood pressure (SBP) of >20mmHg after a meal, occurs frequently in older people and type 2 diabetes (T2DM). Current management of PPH is suboptimal. The magnitude of the postprandial fall in BP is greater when gastric emptying (GE) is relatively more rapid (1). Intravenous administration of glucagon-like peptide-1 (GLP-1) slows GE and attenuates the postprandial fall in BP and rise in splanchnic blood flow in T2DM (2).

Objectives: We evaluated the effects of the prandial GLP-1RA, lixisenatide (LIXI), on GE and the BP, superior mesenteric artery (SMA) blood flow, and glycaemic responses to a 75g oral glucose load in healthy and T2DM subjects.

Methods: 15 healthy subjects (9M, 6F; age: 67.2 ± 2.3yr) and 15 T2DM patients (9M, 6F; age: 61.9 ± 2.3yr) had measurements of GE, BP, SMA blood flow and plasma glucose for 180min after a radiolabelled 75g glucose drink on 2 separate days. All subjects received LIXI (10mcg sc) or placebo (PLAC) in a randomised, double-blind, crossover fashion 30min before the drink.

Results: LIXI slowed GE (Retention at 120min) (P<0.01) and attenuated the fall in SBP (AUC 0-120min) (P<0.001) compared to PLAC in healthy subjects and T2DM, with no difference between the groups. The maximum rise in SMA flow was attenuated by LIXI in both the healthy subjects and T2DM (P<0.01), but was greater in the healthy subjects than T2DM on both PLAC and LIXI days (P<0.001). Plasma glucose (iAUC 0-120min) was greater in T2DM (P<0.005) than healthy subjects, and reduced by LIXI in both groups (P<0.001).

Conclusions: In health and T2DM, the marked slowing of GE and consequent reduction in glycaemia induced by lixisenatide are associated with attenuation of the rise of SMA flow and fall in SBP. Accordingly, lixisenatide may be useful in the management of PPH.

  1. Jones KL, Tonkin A, Horowitz M, Wishart JM, Carney BI, Guha S, Green L. Rate of gastric emptying is a determinant of postprandial hypotension in non-insulin-dependent diabetes mellitus. Clin Sci 1998;94:65-70.
  2. Trahair LG, Horowitz M, Stevens JE, Feinle-Bisset C, Standfield S, Piscitelli D, Rayner CK, Deane AM, Jones KL. Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes. Diabetologia 2015;58:1769-78.