Type 2 Diabetes
Conditions
Brief summary
To perform a study that investigates the effectiveness of adding the SGLT2 inhibitor dapagliflozin + the dipeptidyl peptidase 4 (DPP-4) inhibitor saxagliptin vs placebo to revert from a BBIT regimen to a BOT regimen in patients with type 2 diabetes.
Detailed description
This will be a phase IV study investigating the efficacy and safety of adding the SGLT2 inhibitor dapagliflozin together wih the DPP-4 inhibitor saxagliptin to an intensified insulin treatment regimen. Because BOT is superior to BBIT in respect to the development of bodyweight, hypoglycaemia and patient satisfaction in type 2 diabetes, we hypothesize that the combined addition of the SGLT2 inhibitor dapagliflozin with the DPP-4 inhibitor saxagliptin is effective and safe to revert from a BBIT to a BOT treatment regimen.
Interventions
DRUGDapagliflozin 10 mg + Saxagliptin 5 mg
24 weeks intervention with Dapagliflozin 10 mg + Saxagliptin 5 mg
DRUGPlacebo 1 10 mg + Placebo 2 5 mg
24 weeks intervention with Placebo 1 10 mg + Placebo 2 5 mg
Sponsors
University Hospital Tuebingen
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Age 18 - 75 years * Anti-GAD antibodies negative (Glutamic Acid Decarboxylase) * C-peptide levels ≥ 1.5 ng/mL * Fasting blood glucose \> 126 mg/dl * HbA1c 8.0 - 10.5 % * BMI 25.0 - 45.0 kg/m2 * Previous therapy with BBIT (basal insulin and at least once daily bolus insulin)
Exclusion criteria
* Use of any oral antidiabetic treatment except for metformin (i.e., sulphonylureas, DPP-IV inhibitors, thiazolidinediones, SGLT-2 inhibitors (Sodium dependent glucose transporter) or GLP-1 analogues (glucagone like peptide) within the last three months prior to Screening * Repeated episodes of severe hypoglycaemia within the last six months prior to Screening * History of diabetic ketoacidosis, precoma diabetica, or diabetic coma * Treatment with any other investigational drug within the last three months before Screening * Acute infections within the last four weeks prior to Screening * Recurrent urogenital infections * History of pancreatitis * Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures * History of severe or multiple allergies * Concomitant participation in other clinical trials * Type 1 diabetes * Cardiovascular disease Clinically relevant ventricular tachycardia or ventricular fibrillation, 3rd degree AV block or Torsades de Pointes or treatment with antiarrhythmic drugs. Percutaneous coronary intervention within the past 6 months. Any of the following within the past 6 months: myocardial infarction (MI), coronary artery bypass surgery; unstable angina; or stroke. Uncontrolled unstable angina pectoris or history of pericarditis, myocarditis, endocarditis. Congestive heart failure NYHA (New York Heart Association) class III or IV. Increased risk of thromboembolism, e.g. subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator. * Malignancy including leukemia and lymphoma within the last 5y. * Liver disease such as cirrhosis or chronic active hepatitis. * Significant renal dysfunction (see also
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects achieving a HbA1c ≤ 7.5% and having a reversal from a BBIT to a BOT regimen | 24 weeks | Percentage of subjects achieving a HbA1c ≤ 7.5% and having a reversal from a BBIT to a BOT regimen with treatment of dapagliflozin/saxagliptin or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in hypoglycaemic events between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in daily insulin dose between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in bodyweight between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in body fat content between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in body fat distribution between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in liver fat content between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in intra-nasal insulin-induced brain fMR (functional magnetic resonance) imaging results between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in blood pressure between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in the blood lipid profile between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in microalbuminuria between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in well being and disease perception between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in fear of hypoglycemia between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in HbA1c between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in fasting blood glucose between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
Other
| Measure | Time frame | Description |
|---|---|---|
| changes in (Interleucin 1?ßß) IL-1ß levels between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in Il-6 levels between groups | 24 weeks | treatment of dapagliflozin/saxagliptinn or placebo |
| differences in adverse events between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| differences in severe adverse events between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| differences in heart rate between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| differences in ECG parameters between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in clinical chemistry/haematology parameters between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in adiponectin levels between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
| changes in fetuin-A levels between groups | 24 weeks | treatment of dapagliflozin/saxagliptin or placebo |
Countries
Germany
Outcome results
None listed