SGLT2 antagonists and GLP1 agonists are used since a relatively short period as second line therapy if indicated and are well tolerated by patients featuring low risk of hypoglycaemia in comparison to insulin or other oral glucose lowering drug. This new treatment options offer an effective modality to lower blood glucose, if first line therapeutics fail. According to national and international guidelines combination of oral glucose lowering drugs is possible in multiple ways, but is currently not recommended for GLP1 agonists and SGLT2 inhibitors yet, as evidence and supporting studies are missing proving efficacy and safety\]. Thus studies under standardized conditions are urgently needed to answer these unsolved questions. First results of a combination of a SGLT2 Inhibitor and a GLP1 agonist demonstrated huge potential regarding glucose and weight reduction and safety issues. However, further studies are necessary to elucidate potential mechanisms of combination therapy with SGLT2 inhibitors and GLP1 agonists and its effect on weight loss, glucose control, effects on incretins and adipokines, as well as further effects on ectopic lipid accumulation in liver and other tissues as myocard or pancreas in humans. As both monotherapies have effects on weight and metabolism, changes in abdominal, subcutaneous, hepatic, myocardial or pancreatic lipid content might be speculated and are focus of interest in this study. Recently GLP1 agonists were shown to have effects on hepatic lipid reduction in humans with diabetes. Hepatic lipid content and steatosis hepatis are widely discussed to have major effects on progression of diabetes and cardiovascular disease. Thus reduction of lipid accumulation in hepatic tissue might have an effect on diabetes progression. Also higher myocardial lipid accumulation is seen in diabetic patients probably partly responsible for higher cardiovascular risk in diabetics. So far results combining these two drug classes show less weight loss as might have been expected using monotherapy, so that further investigation will definitely shed light on combination of therapeutic concepts. Facing a multiple of positive side effects (weight loss, blood pressure lowering, potential protective cardiac effects) using a combination of SGLT2 and GLP1 seems to be a promising therapeutic option in diabetic subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
34
Exenatide will be combined with Dapagliflozin
Exenatide matching Placebo will be combined with Dapagliflozin
Dapagliflozin, in both arms
Abt. für Endokrinologie & Stoffwechsel, Univ. Klin f. Innere Medizin III
Vienna, Austria
change in hepatic lipid content measured with magnetic resonance spectroscopy in %
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 despite oral therapy.
Time frame: baseline - week 24
change in myocardial lipid content measured with magnetic resonance spectroscopy in %
to investigate the effects on myocardial 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 despite oral therapy.
Time frame: baseline - week 24
change in pancreatic lipid content measured with magnetic resonance spectroscopy in %
to investigate the effects on pancreatic 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 despite oral therapy.
Time frame: baseline - week 24
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
safety and tolerability from baseline to end by number of participants with treatment related AEs and SAEs
Time frame: baseline- week 24
Quality of Life questionnaire
change from baseline in quality of live assessed by WHO Well Being Index
Time frame: baseline - week 24
change in insulin resistance
change from baseline in insulin resistance assessed by HOMA IR Index
Time frame: baseline - week 24
change in insulin sensitivity
change from baseline in insulin sensitivity assessed by OGIS
Time frame: baseline - week 24
energy expenditure
change from baseline of energy expenditure assessed by indirect calorimetry
Time frame: baseline -week 24
energy intake
change from baseline of energy intake assessed by 3 day eating protocols
Time frame: baseline -week 24
blood pressure
To assess the effect of combination therapy with dapagliflozin and exenatide on blood pressure compared to dapagliflozin and placebo.
Time frame: baseline - week 24
weight loss
To assess the effect of combination therapy with dapagliflozin and exenatide on weight loss compared to dapagliflozin and placebo.
Time frame: baseline - week 24.
change in glomerular filtration rate
change in GFR from baseline
Time frame: baseline -week 24
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