Low dosE GlibENclamide and Dapagliflozin in type 1 Diabetes (LEGEND-D)
For more info please contact cru@ocdem.ox.ac.uk
STUDY OVERVIEW
Type 1 diabetes (T1D) affects around 400,000 people in the UK. It is caused by near-complete loss of insulin-producing cells in the pancreas. It can be challenging to achieve good control of blood glucose throughout the day, in part because of impaired release of hormones other than insulin, such as glucagon.
Glibenclamide and dapagliflozin are medications normally used in the management of type 2 diabetes. They work by increasing the amount of insulin released by the pancreatic beta-cells and helping the body dispose of glucose via the kidneys, respectively.
The LEGEND-D trial aims to find out whether low doses of glibenclamide or a single dose of dapagliflozin could have a new role in T1D by restoring appropriate glucagon release.
STUDY DESIGN
As described in the Participant Information Sheet (PIS), the LEGEND-D trial is a pilot, randomised cross-over, single-centre, non-blinded, clinical trial which will recruit 20 people with T1D and a control group of 10 people without diabetes. Those with T1D will receive a liquid form of glibenclamide and later a single tablet of dapagliflozin, and undergo 5 controlled hypoglycaemia challenges; the control group without diabetes will not receive any medication and will undergo one hypoglycaemia challenge. The diagram of the trial visits for both diabetic and non-diabetic participants is illustrated below. All trial activities will be conducted by the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) Clinical Research Unit (CRU) at the Churchill Hospital.
A diagram showing the randomisation options for the LEGEND-D Trial
AIMS
PRIMARY:
To determine whether treating people with T1D for 14-18 days with glibenclamide at 0.3mg, 0.6mg or 3mg daily can increase plasma glucagon levels during induced hypoglycaemia compared to before treatment.
SECONDARY:
To compare changes in a) plasma glucagon and b) plasma somatostatin before and after administration of a single dose of dapagliflozin in T1D participants to that of participants without diabetes.