Dapagliflozin During Exercise for the PrevenTion of Hypoglycaemia
Status:
Suspended
Trial end date:
2021-12-22
Target enrollment:
Participant gender:
Summary
There are approximately 400,000 people in the UK who are living with type 1 diabetes (T1DM),
of whom 29,000 are children.
People with T1DM experience on average 2 episodes of symptomatic hypoglycaemia per week , and
exercise (especially aerobic) increases this risk . Strategies to prevent hypoglycaemia
during and after exercise include increasing glucose consumption and reducing insulin dose,
however overcompensation may result in worsening of blood glucose control.
Dysregulated glucagon secretion, manifested as a reduced counter-regulatory response during
hypoglycaemia, is a key feature in T1DM, occurring soon after diagnosis.
Anecdotal evidence suggests that SGLT-2 (sodium/glucose cotransporter-2) inhibitors (SGLT2i)
such as dapagliflozin prevent exercise-induced hypoglycaemia in T1DM. SGLT2is promote glucose
excretion without causing hypoglycaemia.Paradoxically, given their mode of action, they
increase plasma glucose and stimulate glucagon secretion. Studies in diabetic rats indicate
that the physiological counter-regulatory response is suppressed in insulin-treated diabetes,
a defect that can be corrected by somatostatin antagonists.
The DEPTH trial will test the novel hypothesis that hypoglycaemia results from hypersecretion
of somatostatin, and that this defect can be corrected by SGLT2i. As these medications are
already in clinical use, our findings may be rapidly translated into practice. Understanding
these key processes has the potential to generate novel therapeutic strategies to improve
glycaemic control, thereby facilitating a more active lifestyle in people with T1DM.
Phase:
Phase 2
Details
Lead Sponsor:
University of Oxford
Collaborators:
Oxford Brookes University The Leona M. and Harry B. Helmsley Charitable Trust