CompletedPhase IIInterventional

Low dosE GlibENclamide and Dapagliflozin in type 1 Diabetes (LEGEND-D)

Living with type 1 diabetes means constantly balancing insulin and food to avoid dangerous dips in blood sugar, known as 'hypos'. Normally, the body releases a hormone called glucagon to raise blood sugar when it drops too low, but this natural safety net stops working properly in type 1 diabetes. Researchers at the University of Oxford are testing whether two existing medicines, glibenclamide and dapagliflozin, can switch this safety system back on. In this study, volunteers with type 1 diabetes take low doses of these medicines and undergo closely supervised tests to see how their bodies react when blood sugar dips. A group of volunteers without diabetes will also take part for comparison. The goal is to discover new ways to help people with type 1 diabetes prevent severe hypos in the future.

At a glance

Status

Completed

Phase

Phase II

Sponsor

University of Oxford

Enrolment target

Start

26 Feb 2024

Estimated completion

31 May 2024

Type 1 diabetes mellitus

What is this study about?

In type 1 diabetes, the body cannot make insulin, so people must take insulin every day to keep their blood sugars balanced. However, insulin can sometimes cause blood sugar levels to fall dangerously low, causing what is commonly known as a 'hypo'. In a healthy body, another hormone called glucagon steps in like a backup brake, raising blood sugar back up to safe levels. In type 1 diabetes, this glucagon backup system often stops working, leaving people vulnerable to sudden hypos.

Doctors are searching for treatments that can restore this natural glucagon response. Earlier research in laboratory settings and in type 2 diabetes suggests that two medicines—glibenclamide and dapagliflozin—might gently stimulate the cells that make glucagon. When used at very low doses, these drugs may help kick-start glucagon release without causing unwanted drops in blood sugar.

The LEGEND-D trial is testing whether this approach works in people living with type 1 diabetes. By comparing people who have type 1 diabetes with a comparison group of healthy volunteers, the study team hopes to understand the biology of hypos much better.

While this study is not guaranteed to change your personal treatment right away, its findings could open the door to brand-new treatments designed to protect people with type 1 diabetes from severe, frightening hypos in everyday life.

Key takeaways

Tests whether low doses of two existing medicines can help prevent hypos in type 1 diabetes.
Open to adults aged 18 to 75 with type 1 diabetes, as well as healthy volunteers without diabetes.
Involves hospital visits in Oxford with closely supervised, controlled blood sugar tests.
Participants with diabetes receive detailed continuous glucose monitoring reports.
Taking part is entirely voluntary, and you can withdraw at any time.

Who may be eligible?

This trial is open to adults aged 18 to 75. Researchers are looking for two groups of people: adults diagnosed with type 1 diabetes for at least one year, and healthy volunteers without diabetes to act as a comparison group.

To take part in the diabetes group, you should be using multiple daily injections or an insulin pump, and your recent long-term blood sugar level (HbA1c) must be below 10% (86 mmol/mol). You will also need to be familiar with managing hypos. You will not be able to join if you have had diabetic ketoacidosis (DKA) in the last month, more than one severe hypo needing emergency help in the past year, or active eye problems linked to diabetes.

For safety reasons, volunteers in both groups cannot take part if they have significant heart conditions, severe high blood pressure, kidney or liver problems, a history of seizures, or if they are pregnant or breastfeeding. Certain heart medications, such as beta-blockers, are also not permitted during the study.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you between 18 and 75 years old?
Have you had type 1 diabetes for at least 12 months, or do you have no history of diabetes?
If you have diabetes, is your HbA1c below 10% (86 mmol/mol)?
Are your heart, kidneys, and liver in generally good health?
Are you not currently pregnant or breastfeeding?
Are you free from recent severe hypos or ketoacidosis in the past month?

Answer every question to see your result.

What does participation involve?

If you take part and have type 1 diabetes, your involvement will last around 8 to 10 weeks, split into four separate two-week blocks. You do not have to do these blocks back-to-back. During the study, you will take a liquid medicine called glibenclamide daily for up to 54 days, along with a single dose of dapagliflozin. You will also attend five closely monitored hospital tests where doctors gently lower your blood sugar in a safe, controlled way for 40 minutes to measure your hormone levels. You will wear a continuous glucose monitor (FreeStyle Libre) during the trial, and the team will give you reports showing your daily blood sugar patterns. Volunteers without diabetes will attend just one controlled test session without taking any ongoing medication.

Potential risks and benefits

This trial may not provide direct health benefits to you, but you will receive detailed printouts of your blood sugar readings and you will be helping researchers find better ways to protect people from hypos in the future. The main risk is experiencing the unpleasant feelings of a low blood sugar during the supervised hospital tests, such as shakiness, sweating, or a fast heartbeat. However, medical staff will watch you continuously and can restore your blood sugar quickly using glucose. Taking blood samples may also cause mild bruising or dizziness. Taking part is completely voluntary, and you are free to leave the trial at any point without it affecting your usual NHS medical care.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM)
City only
Oxford, England

Common questions

Will taking part cure my type 1 diabetes?

No. The medicines being tested are not a cure. The researchers are studying whether they can help your body release glucagon to defend itself against low blood sugars.

Is the low blood sugar test safe?

Yes. While having a hypo feels unpleasant, the tests are done in a hospital under constant expert supervision. Your blood sugar is checked every five minutes, and staff can raise your levels back to normal instantly.

Do I have to stop taking my normal insulin?

No, you will continue your regular diabetes care alongside the study, although the research team will guide you on how to manage your insulin during the test visits.

Can I take part if I do not have diabetes?

Yes. The trial needs healthy adult volunteers without diabetes to act as a comparison group for a single test visit.

What happens if I change my mind after joining?

You are free to stop participating at any time. You do not need to give a reason, and your regular NHS medical care will not be affected in any way.

How to find out more

Nkemjika Abiakam

legend-d@dtu.ox.ac.uk +44 (0)1865 857244 ext 244 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.