Effects of Combined Dapagliflozin and Exenatide Versus Dapagliflozin and Placebo on Ectopic Lipids in Patients With Uncontrolled Type 2 Diabetes Mellitus.
Condition: Steatosis, Liver; Type2 Diabetes
MeSH terms: Fatty Liver; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    


Intervention name(s): Exenatide; Exenatide matching Placebo; Dapagliflozin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Exenatide will be combined with Dapagliflozin; Exenatide matching Placebo will be combined with Dapagliflozin; Dapagliflozin, in both arms
Intervention MeSH terms: Dapagliflozin; Exenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: SGLT2 inhibitor; GLP1 agonist; type 2 Diabetes; steatosis of the liver; ectopic lipids; combined therapy