Dapagliflozin + Saxagliptin in a Basal-bolus Insulin Treatment
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: Placebo 1 10 mg + Placebo 2 5 mg
- Registration Number
- NCT02965443
- Lead Sponsor
- University Hospital Tuebingen
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
- 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)
- 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 exclusion criteria laboratory abnormalities).
- State after kidney transplantation
- Endocrine disease:
Acromegaly or treatment with growth hormone or similar drugs. Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 8 weeks; thyroid hormone replacement is allowed if the dosage has been stable for at least 3 months and the TSH is within normal limits
•Any of the following significant laboratory abnormalities: eGFR (as calculated by the MDRD equation) < 60 ml/min at Screening Fasting triglycerides >700 mg/dl (>7.9 mmol/l)
- Systolic blood pressure outside the range of 100-160 mmHg or diastolic blood pressure above 95 mmHg at Screening
- History of active substance abuse (including alcohol > 40g/day) within the past 2 years.
- Pregnancy or childbearing potential without adequate contraception
- Present therapy with systemic steroids
- Presence of psychiatric disorder or intake of anti-depressive or anti-psychotic agents with the exception of benzodiazepines and SSRIs/SNRI´s (selective serotonin reuptake inhibitor)
- Potentially unreliable subjects, and those judged by the investigator to be unsuitable for the study.
- Contraindications for Magnetic resonance (MR) scanning such as persons with cardiac pacemaker and implants out of metal or claustrophobia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Verum Dapagliflozin 10 mg + Saxagliptin 5 mg Dapagliflozin 10 mg + Saxagliptin 5 mg, each once daily, for 24 weeks Placebo Placebo 1 10 mg + Placebo 2 5 mg Placebo 1 10 mg + Placebo 2 5 mg, each once daily, for 24 weeks
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method changes in daily insulin dose 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 fasting blood glucose 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 body fat content 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 hypoglycaemic events 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 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 body fat distribution 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
Trial Locations
- Locations (1)
University Hospital Tübingen
🇩🇪Tübingen, Germany