DECREASE: Dapagliflozin Plus Exenatide on Central REgulation of Appetite in diabeteS typE 2
Condition: Type 2 Diabetes Mellitus; Obesity
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a 16 week, phase 4, randomized and placebo controlled trial, investigating the
      separate and combined effects of Sodium Glucose coTransporter 2 (SGLT2) inhibition with
      dapagliflozin and Glucagon Like peptide-1 (GLP-1) receptor agonism with exenatide on food
      intake, body weight and the neural activity in the central satiety and reward circuits in
      response to food-related stimuli by blood oxygen level-dependent (BOLD) fMRI in obese type 2
      diabetes patients. The investigators hypothesize that treatment with SGLT2 inhibitors is
      associated with alterations in central reward and satiety circuits in response to food
      related stimuli, leading to increased appetite and food intake. In addition, the
      investigators hypothesize that adding a GLP-1 receptor agonist to the treatment with an SGLT2
      inhibitor may increase weight loss and prevent the increased food intake during treatment
      with SGLT2 inhibitors due to effects on neuronal activity of central satiety and reward
      circuits in response to food-related stimuli in obese patients with T2DM.
    

Detailed description: 
      The aim of this study is to investigate 1) the seperate and 2) combined actions of SGLT2
      inhibition and GLP-1 receptor agonism on food intake, body weight and the activity within the
      central satiety and reward circuits in response to food-related stimuli and 3) wheter the
      combination with a GLP-1 receptor agonist can prevent the increased intake observed with
      SGLT2- inhibition treatment.

      Methods: In four groups of obese patients with T2DM (n=16 per group), food intake and
      neuronal activity in relevant CNS circuits in response to food-related stimuli (using fMRI)
      will be investigated during 16 week treatment in a double blind placebo-controlled randomized
      trial with:1) SGLT2 inhibitor dapagliflozin 10 mg/day in combination with placebo GLP-1
      receptor agonist exenatide twice daily, 2) GLP-1 receptor agonist exenatide twice daily in
      combination with placebo dapagliflozin, 3) combination of dapagliflozin 10 mg/day and
      exenatide twice daily, or 4) placebo dapagliflozin and placebo exenatide twice daily. To
      correlate changes in brain activity with subsequent feeding behavior, the investigators will
      measure food intake, self-reported hunger, satiety and mood, during a choice-buffet after the
      scanning.

      Expected results: This project will gain insight into the CNS mechanisms underlying the the
      effects of seperate and combined treatment with SGLT2 inhibition and GLP-1 receptor agonism.
      Furthermore, this project will provide insight if combined treatment with a GLP-1 receptor
      agonist will prevent the increased intake, observed by treatment with an SGLT2 inhibitor, and
      if so, in the underlying (CNS) mechanisms. These findings may increase the understanding of
      the development of obesity and weight loss problems in obese and T2DM patients and may
      support the development of a balanced SGLT2 inhibitor/GLP-1 receptor agonist combination as a
      treatment strategy for obesity and T2DM.
    

Intervention name(s): Dapagliflozin 10mg; Exenatide; placebo exenatide; placebo dapagliflozin
Intervention type(s): Drug; Drug; Other; Other
Intervention description(s): Dapagliflozin 10mg oral tablet once daily; Exenatide 5 microgram b.i.d. week 1-4 Exenatide 10 microgram b.i.d. week 5-16; placebo b.i.d. exenatide; placebo tablets dapagliflozin
Other intervention name(s): SGLT2 inhibitor ; Forxiga; GLP-1 receptor agonist ; Byetta
Intervention MeSH terms: Dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Exenatide
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: SGLT2 inhibition; dapagliflozin; GLP-1 receptor agonist; exenatide; Central satiety and reward circuits; bodyweight; brain