The glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, inhibits small intestinal motility, flow, transit and absorption of glucose in health and type 2 diabetes: a randomised controlled trial.  — ASN Events
  1. Schedule
  2. ADS Clinical Orals: Gut and Glycaemia
  3. The glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, inhibits small intestinal motility, flow, transit and absorption of glucose in health and type 2 diabetes: a randomised controlled trial. 

The glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, inhibits small intestinal motility, flow, transit and absorption of glucose in health and type 2 diabetes: a randomised controlled trial.  (#71)

Chinmay S Marathe 1 , Sony S Thazhath 2 , Tongzhi Wu 1 , Jessica Chang 1 , Joan Khoo 3 , Paul Kuo 4 , Helen Checklin 2 , Michelle Bound 2 , Rachael Rigda 2 , Benjamin Crouch 5 , Karen Jones 2 , Michael Horowitz 1 , Christopher K Rayner 2 4
  1. Discipline of Medicine , Endocrine & Metabolic Unit, Royal Adelaide Hospital / University of Adelaide , Adelaide , SA, Australia
  2. Discipline of Medicine , University of Adelaide / Royal Adelaide Hospital , Adelaide , SA , Australia
  3. Department of Endocrinology, Changi General Hospital , Singapore
  4. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital , Adelaide , SA , Australia
  5. Department of Nuclear Medicine, PET and Bone Densitometry, Royal Adelaide Hospital, Adelaide, SA, Australia

The GLP-1 receptor agonist, exenatide, reduces postprandial blood glucose in type 2 diabetes in part by slowing gastric emptying. However, its impact on small intestinal function is unknown.

Our aim was to determine the acute effects of intravenous exenatide on small intestinal motility, flow events, and transit, and glucose absorption, following intraduodenal glucose infusion.

10 healthy subjects (8 male, 2 female; mean age 37 ± 5yrs; BMI 27.4 ± 1.7 kg/m2) and 10 patients with diet-controlled type 2 diabetes (7 male, 3 female; mean age 60.4 ± 2.3 yrs; BMI 29.1±1.5 kg/m2, HbA1c 6.1 ± 0.2 %) received intravenous exenatide (7.5mcg) or saline control (T= -30 to 240min) in a double-blind randomised crossover design. Glucose (45g), together with 5g 3-O-methylglucose (3- OMG) and 20MBq99mTc-sulphur-colloid (total volume 200ml), was given intraduodenally (T=0 to 60min; 3kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter, and small intestinal transit using scintigraphy. Blood was sampled for blood glucose, serum 3-OMG (an index of glucose absorption), and plasma insulin and C-peptide concentrations.

Results are shown (table). In health and type 2 diabetes, duodenal pressure waves and antegrade flow events were fewer with exenatide compared to control. Mean duodeno-caecal transit time with control was 121 (95% CI: 98 - 144) min in health and 120 (95% CI: 85 - 155) min in type 2 patients, but transit was markedly delayed with exenatide, such that the radiolabel did not reach the caecum within 240 min in any subject. Blood glucose and serum 3-OMG concentrations were lower with exenatide than control. Insulin and C-peptide concentrations were initially lower with exenatide than control, and subsequently higher. Nausea was greater in health and diabetes with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea.

In conclusion, intravenous exenatide acutely suppresses small intestinal motility, flow events, and transit, and reduces the rate of glucose absorption, in both health and type 2 diabetes, suggesting that changes in small intestinal motor function, and thereby glucose absorption, contribute to the lowering of postprandial glycaemia by GLP-1 receptor agonists.

2071-table%20ads%20ex%20si%20motility%2026.5.15%20cm%20.jpg