dapagliflozin + saxagliptin in a basal-bolus insulin treatment

Conditions: Type 2 Diabetes

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.

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.

Eligibility criteria:
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 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) \ 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