Effects of Combined Dapagliflozin and Exenatide Versus Dapagliflozin and Placebo on Ectopic Lipids in Patients With Uncontrolled Type 2 Diabetes Mellitus.

Sponsor
Medical University of Vienna
Study ID
NCT03007329
Phase
PHASE4
Status
Completed

Conditions

  • Steatosis, Liver
  • Type2 Diabetes

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Exenatide — DRUG
    Exenatide will be combined with Dapagliflozin
  • Exenatide matching Placebo — DRUG
    Exenatide matching Placebo will be combined with Dapagliflozin
  • Dapagliflozin — DRUG
    Dapagliflozin, in both arms

Study Details

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.

Key Dates

Start date
Mar 8, 2017
Status verified
Apr 2022
Primary completion
Nov 26, 2019
Completion
Jan 16, 2020

Study Design

Enrollment
34 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Dapagliflozin & Exenatide
    Dapagliflozin 10mg orally once daily \& Exenatide 2mg subcutaneous once weekly
  • Placebo Comparator: Dapagliflozin & Placebo
    Dapagliflozin 10mg orally once daily \& Exenatide matching Placebo 2mg subcutaneous once weekly

Primary Outcome Measure

change in hepatic lipid content measured with magnetic resonance spectroscopy in % [ Time Frame: baseline - week 24 ]

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