Efficacy of combination of Exenatide and Dapagliflozin compared to Dapagliflozin and Placebo and its effects on hepatic, myocardial and pancreatic fat distribution in patients with type 2 diabetes mellitus
Conditions
Interventions
Trade Name: Forxiga
Product Name: Forxiga
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN
CAS Number: 461432-
Sponsors
Medical University Vienna, Gender Medicine Unit, Div. of Endocrinology, Dep of Medicine III
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: T2DM Sex: male and female HbA1c >=6.5 and =18 and =25kg/m² Metformin>=1000mg daily, 8 weeks stable dose Please note: Type 2 diabetes mellitus patients treated with less than 1000 mg metformin per day can only be included if the investigator considers the patient to be on the maximum tolerated dose and the investigator has documented the reason why uptitration to 1000 mg was not possible able and willing to not change diet and physical activity during enrolement in study consent and able to give informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: other diabetes diagnosis than T2DM patients on other antidiabetic medication (Sulfonylurea, Glitazone, insulin for more than 2 weeks (see below), SGLT2 inhibitors, GLP1 agonist, nateglinid, repaglinid, acarbose, DPP4 inhibitors) Subjects currently or previously treated with insulin (with the exception of emergency situations in which insulin was given for less than 14 consecutive days, but not within the last 3 months before screening) known intolerance against study medication Contraindications including hypersensitivity known to metformin according to the local label recurrent urinary tract infections GFR < 60 Liver enzymes above 3 fold normal range Bilirubin higher 3 fold normal range Any other clinical condition that would jeopardize patients safety while participating in this clinical trial disease at screening (other than NAFLD) such as relevant cardiovascular, gastrointestinal, hepatic, neurologic, psychiatric, endocrine (i.e. pancreatic) except T2DM, hematologic, malignant, infection or other major systemic diseases making implementation of the protocol or interpretation of the study results difficult history of pancreatitis Known autoimmune disease or chronic inflammatory condition Myocardial infarction or stroke within 6 months prior to screening Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g.malaria, babesiosis, haemolytic anaemia) Other liver disease including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology malignancy within the last 5 years before randomisation medullary thyroid cancer family history of multiple endocrine neoplasia syndrome Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake Presence of any absolute or relative contraindication for the conduct of an MRI investigation, such as cardiac pacemakers, ferromagnetic haemostatic clips in the central nervous system,metallic splinters in the eye, ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators, cochlear implants, insulin pumps and nerve stimulators, prosthetic heart valves etc. History of bariatric surgery Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight Subjects receiving antihypertensive medication and/or thyroid hormones, the dose(s) of which have not been stable for at least 6 weeks prior to baseline Current treatment with systemic steroids at time of informed consent (Treatment with local and inhaled steroids is allowed) Use of drugs potentially associated with NAFLD for more than 2 consecutive weeks in the 6 months prior to sc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint for the efficacy analysis is the liver fat [measured in percent] content at the end of the treatment period.;Timepoint(s) of evaluation of this end point: baseline and 24 weeks;Main Objective: to investigate the effects on hepatic lipid content reduction of combination therapy with dapagliflozin (10mg daily) and exenatide (2mg weekly) compared to dapagliflozin (10mg daily) and placebo given for 24 weeks in patients with type 2 diabetes mellitus and insufficient glycaemic control.; Secondary Objective: to investigate the effects on myocardial, pancreatic, abdominal and visceral lipid content reduction to assess safety and tolerability of combination therapy with dapagliflozin and exenatide compared to dapagliflozine and placebo. To assess effect of combination therapy with dapagliflozin and exenatide on quality of live and diabetes managment safisfaction compared to dapagliflozine and placebo. To assess the effect of combination therapy with dapagliflozin and exenatide on glycaemic control, insulin resistance, blood pressure, glucagon level, weight loss and kidney function compared to dapagliflozine and placebo. To assess the effect of combination therapy with dapagliflozin and exenatide on eating pattern, energy intake and expenditure, compared to dapagliflozine and placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are measurements on change in body fat , liver volume, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue and total lean tissue, myocardial and pancreatic fat from baseline to week 24 measured by MRI, the change in HbA1c from baseline after 24 weeks of treatment, the change in body weight from baseline after 24 weeks of treatment, the occurrence of confirmed symptomatic hypoglycaemic events during 24 weeks, the change in blood pressure (SBP and DBP) from baseline, after 24 weeks. Other exploratory endpoints are the occurrence of treat to target efficacy i.e. HbA1c 5% and >10% ) from baseline after 24 weeks of treatment, the change in insulin sensitivity and Insulin secretion, as well as glucose effectivness assessd by oGTT from baseline after 24 weeks of treatment, the change in glucagon levels, from baseline after 24 weeks of treatment, the change in energy intake and expenditure from baseline after 24 weeks of treatment, Sex/Gender differences in lipid accumulation, weight loss, glycaemia and the effect of combined treatment on changes. the change in kidney function assessed by GFR from baseline after 24 weeks of treatment Safety and tolerability endpoints Safety of the treatment will be evaluated by AEs, laboratory tests, vital signs and ECG. All subjects who received at least one dose of treatment will be included in the safety evaluation. ;Timepoint(s) of evaluation of this end point: baseline and 24 weeks | — |
Countries
Austria
Contacts
Public ContactMedical University Vienna
Medical University Vienna
Outcome results
None listed