Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

Radboud University Medical Center

Status and phase

Completed

Phase 3

Phase 2

Conditions

Hypoglycemia

Diabetes Mellitus, Type 1

Treatments

Drug: Placebo

Drug: Exenatide

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02735031

ESR-15-10862

Details and patient eligibility

About

Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired hypoglycaemic awareness (IHA) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IHA is usually the end-result of a process of habituation to recurrent hypoglycemia that is potentially reversible. Treatment with glucagon-like peptide (GLP)-1 Receptor Agonists (1RAs) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the GLP-1RA, exenatide, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IHA. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 6 weeks with exenatide (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.

Enrollment

10 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Type 1 diabetes, disease duration >1 year
Age >18 years, <70 years
Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
Impaired hypoglycaemic awareness as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire
Glycated haemoglobin (HbA1c) ≥42 mmol/mol (6%) and ≤75 mmol/mol (9.0%)
Ability to provide informed consent

Exclusion criteria

Treatment with incretin-based therapy
Known intolerance to GLP-1RAs (including allergy)
Treatment with glucose-modifying or immune-modifying agents, e.g. prednisolon
Recent history of myocardial infarction or stroke (past year) or laser coagulation for proliferative retinopathy (past 6 months)
Proliferative retinopathy
Symptomatic diabetic neuropathy
Diabetic nephropathy as reflected by albumin-creatinin ratio >30 mmol/mg or estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2
Known heart failure
History of pancreatitis (acute or chronic) or pancreatic cancer
Body-mass index >40 kg/m2
Use of premixed insulin or of long-acting insulin alone
Total daily insulin dose requirements <20 units unless on pump treatment
Pregnancy or unwillingness to undertake measures for birth control