None listed
Conditions
Brief summary
Gastric emptying (GE), which exhibits a wide inter-individual variation, determines the rate of exposure of nutrients (including carbohydrates) to the small intestine, where they are absorbed into the circulation. Insulin-induced hypoglycaemia (~2.5 mmol/L) accelerates gastric emptying substantially in both health and diabetes. The major mechanism for lowering of postprandial glycaemia by GLP-1 receptor agonists is by slowing gastric emptying. Although GLP-1RAs themselves are associated with minimal risk of hypoglycaemia (since their insulinotropic effects are glucose-dependent), the risk of hypoglycaemia is increased substantially when GLP-1RAs, especially short-acting, are combined with exogenous insulin or insulin secretagogues. Our aim is to determine whether treatment with short-acting GLP-1RAs, attenuates the acceleration of gastric emptying during insulin-induced hypoglycaemia in patients with type 2 diabetes.
Interventions
Short acting GLP-1 receptor agonist, exenatide twice daily OR placebo
a) exenatide dose 10microgram twice daily
b) duration of administration: 4 weeks - drug and 4 weeks - placebo
c) Mode of administration - subcutaneous injection
d) monitoring adherence - frequent phone calls during trial period to ensure compliance, checking the number of injections left when participant attends study day at the end of each 4 week period.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Primary purpose
Prevention
Eligibility
Sex/Gender
All
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
• Men and women with type 2 diabetes either diet controlled or metformin alone • Aged 40 - 70 years • Body Mass Index 20-40 kg/m² • HbA1c less than or equal to 8.5 %
Exclusion criteria
• History of type 1 diabetes or on medications other than metformin • HbA1c >8.5 % • History of gastrointestinal disease, including known gastroparesis, peptic ulcer disease, significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) or a history of migraine or panic attacks. • Other significant illness, including epilepsy, cardiovascular or respiratory disease. • Impaired renal function (as assessed by calculated creatinine clearance < 50 mL/min using the Cockcroft-Gault equation) or if iron stores or liver function tests are outside the following normal ranges: - Alanine aminotransferase (ALT) < 110 U/L - Alkaline phosphatase (ALP) 30 - 110 U/L - Aspartate transaminase (AST) < 90 U/L - Total bilirubin 2 - 24 µmol/L - Haemoglobin 130 – 180 g/L (Males) - Haemoglobin 115 – 155 g/L (Females) - Ferritin > 30 µg/L (Males) - Ferritin > 15 µg/L (Females) • Requirement for medication known to influence gastrointestinal function, (e.g. prokinetic drugs [metoclopramide, domperidone, erythromycin], antiemetics [ondansetron], antidiarrhoeals [loperamide], H2 receptor antagonists [ranitidine], drugs with substantial anticholinergic effects [amitriptyline, doxepin, dothiepin, mirtazapine, haloperidol, chlorpromazine, risperidone, oxybutynin], opioids [morphine, oxycodone, codeine], orlistat. • Evidence of drug or alcohol abuse, or consumption of more than 20 g alcohol or 10 cigarettes on a daily basis. • Vegetarian • Donation of blood within the previous 3 months • Participation in any other research studies within the previous 3 months • Previous exposure to radiation for research purposes in the preceding 12 months • Inability to give informed consent • Positive pregnancy status or lactating (breast-feeding) female • Contra-indication to use of exenatide • A known history of intolerance or unwilling to self-inject exenatide
Outcome results
None listed