Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1, Exenatide, Incretins, GLP-1, Insulin
Brief summary
Patients with type 1 diabetes (T1D) depend on insulin therapy as substitution for the lack of endocrine insulin production due to an autoimmune destruction of beta-cells in the pancreatic inslets. Insulin therapy is based on long lasting basal insulin for controlling fasting plasma glucose, and short lasting mealtime insulin for the postprandial plasma glucose. The long term efficacy of this treatment is measured in glycated haemoglobin A1c (HbA1c) of \<7.0% as the treatment goal. Intensive insulin therapy is associated with side effects such as hypoglycaemia, weight gain, and unwanted exaggerated excursions in PPG. This may ultimately affect treatment compliance. The abovementioned problems associated with insulin treatment in T1D can also be seen in insulin-treated patients with type 2 diabetes (T2D). However, in T2D the combination of insulin with glucagon-like peptide-1 (GLP-1) receptor agonist (RA) has proven effective in reducing the weight gain and insulin dose in insulin-treated patients with T2D without exacerbating the risk of hypoglycaemia. Exenatid is a short lasting GLP-1RA approved for treatment in T2D, and the investigators intend to evaluate it in a randomized, controlled trial as add-on therapy to standard insulin therapy for patients with T1D. The investigators hypothesise that the add-on of exenatide to insulin therapy in patients with T1D will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia.
Interventions
DRUGExenatide
DRUGPlacebos
Sponsors
Steno Diabetes Center Copenhagen
Filip Krag Knop
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* T1D according to WHO criteria with duration of ≥1 year * Age ≥18 years * BMI \>22.0 kg/m2 * HbA1c \>7.5% and \<10.0% at visit 0 (screening) * Able to count carbohydrates
Exclusion criteria
* Insulin pump treatment * Hypoglycaemia unawareness (inability to register low blood glucose) * Diabetic gastroparesis * Compromised kidney function (eGFR \<60 ml/min/1.73m2, dialysis or kidney transplantation) * Liver disease with elevated plasma alanine aminotransferase (ALT) \> three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive) * History of acute and/or chronic pancreatitis * Subjects with personal or family history of medullary carcinoma or MEN syndrome * Inflammatory bowel disease * Cancer unless in complete remission for \>5 years * Proliferative retinopathy * Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation * Alcohol/drug abuse * Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives * Pregnant or nursing women * Known or suspected hypersensitivity to trial product or related products * Receipt of an investigational drug within 30 days prior to visit 0 * Simultaneous participation in any other clinical intervention trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | 6 months | Change in HbA1c from baseline to end of study (time 6 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in insulin dosage | 6 months | — |
| changes in body weight | 6 months | — |
| changes in BMI | 6 months | — |
| changes in body composition | 6 months | DXA scan measuring bonemineral density |
| changes in fasting plasma glucose | 6 months | — |
| changes in post prandial plasma glucose | 6 months | — |
| changes in fasting plasma levels of C-peptide | 6 months | — |
| Quality of life self reported | 6 months | Quality of Life Questionaire |
| adverse events (including hypoglycaemic episodes) | 6 months | — |
| dietary patterns | 6 months | Food frequency questionaire three times during the intervention |
| HDL (High Density Lipoprotein) | 6 months | — |
| LDL (Low Density Lipoprotein) | 6 months | — |
| VLDL (Very Low Density Lipoprotein) | 6 months | — |
| hsCRP (High-Sensitivity C-Reactive Protein) | 6 months | — |
| total cholesterol | 6 months | — |
| triglycerides | 6 months | — |
| proBNP (Pro-Brain Natriuretic Peptide) | 6 months | — |
| Treatment satisfaction | 6 months | Diabetes treatment satisfactory questionnaire status version |
Countries
Denmark
Outcome results
None listed