Low dosE GlibENclamide and Dapagliflozin in type 1 Diabetes (LEGEND-D)
Research type
Research Study
Full title
Low dose glibenclamide and dapagliflozin in Type 1 Diabetes Mellitus
IRAS ID
1004710
Contact name
Ioannis Spiliotis
Contact email
Sponsor organisation
University of Oxford
ISRCTN Number
ISRCTN58098350
Research summary
Type 1 diabetes (T1D) affects around 400,000 people in the UK, and is caused by nearly complete loss of insulin-producing cells in the pancreas. Managing blood sugar levels with insulin injections can be challenging in T1D, and very low blood sugar (hypos) are one of the most feared complications. Disruption of other hormones such as glucagon, which raises blood sugar and counter-balances the effects of insulin during hypos, is now also recognised as part of the disorder. How this happens is not clear, and better understanding of this mechanism could lead to treatments aimed at reducing the risk of hypos.
Glibenclamide (sulfonylurea) is a type of anti-diabetic medication which is commonly used to increase the amount of insulin released by the pancreatic beta-cells. Preclinical studies have shown that sulfonylureas can also improve glucagon levels when used in very small doses by working on pancreatic alpha-cells, which release glucagon. In addition, another type of anti-diabetic medication called dapagliflozin has also been shown to work on pancreatic alpha-cells.
We previously conducted a small pilot study (LEGEND-A), which suggested that low doses of glibenclamide (0.3mg/day) could alter glucagon release in some people with type 2 diabetes without increasing the risk of hypos. The aim of this follow-up study (LEGEND-D) is to find out whether similar doses of glibenclamide or a single dose of dapagliflozin could restore glucagon release in people with T1D. It is hoped that add-on therapies such as these may become a new way of helping people with T1D prevent hypo episodes.
The trial will involve 2 groups of participants: a) people with T1D, who will be given a liquid form of glibenclamide for a maximum of 54 days, followed by a single dose of dapagliflozin, and undergo 5 controlled hypoglycaemia challenges (hypo clamp) over 8-10 weeks; b) a control group (non-DM group) without diabetes who will undergo 1 hypoglycaemia challenge without extra medication
REC name
South West - Central Bristol Research Ethics Committee
REC reference
23/SW/0098
Date of REC Opinion
22 Sep 2023
REC opinion
Further Information Favourable Opinion