Effects of Glucagon Like Peptide-1(GLP-1) and Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes
Condition: Obesity; Type 2 Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional

Summary: 
      The aim of this study is to investigate if endogenous Glucagon Like Peptide -1 (GLP-1) has an
      effect on brain satiety and reward systems and if there are alterations in obese patients
      with type 2 diabetes (T2DM). Secondly, the aim is to investigate whether treatment with a
      GLP-1 analog, liraglutide, restores these signals in obese patients with type 2 diabetes.
      Finally, also the endogenous GLP-1 effects will be investigated in obese individuals before
      and after gastric bypass surgery on brain satiety and reward systems.
    

Detailed description: 
      First aim will be addressed in a cross-sectional randomized study. 20 healthy, lean and 20
      obese individuals with type 2 diabetes (T2DM) will be exposed to food cues and with
      concomitant infusion of glucagon Like peptide-1 (GLP-1) receptor antagonist or saline, to
      assess the involvement of endogenous GLP-1, secreted in response to a meal. Measurements
      activation of CNS circuits involved in satiety and reward will be performed using blood
      oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI).

      The second aim will be addressed in cross-over randomized-controlled trial (RCT) in the T2DM
      patients only. Patients will be randomly assigned liraglutide vs insulin glargine treatment,
      during a treatment period of 12 weeks each with a 12-week washout period in between. The
      investigators will perform the same fMRI protocol.

      The third aim will be addressed in a study with obese individuals who are scheduled for a
      gastric bypass surgery. The same protocol as for the first aim will be performed and this
      will be before and after the surgery in the same individuals.
    

Intervention name(s): Liraglutide treatment 12 weeks; insulin glargine treatment; GLP-1 receptor antagonist
Intervention type(s): Drug; Drug; Drug
Intervention description(s): liraglutide will be started with a titration period of 2 weeks: week 1 0.6mg once daily, week 2 1.2mg once daily. If well tolerated, treatment will be continued for 10 more weeks in dosage of 1.8mg once daily; Insulin glargine treatment consist a treatment period of 12 weeks. Treatment will start with a dosage of 10 IU once daily. Patient will self-titrate the insulin glargine dosage based on self-monitored fasting blood glucose (FBG) concentrations for the previous 3 days using the following guideline: If FBG levels are above 5.6 mmol/L (100-153 mg/dL) on 3 consecutive mornings, the daily dose is to be increased by 2 IU/day. If hypoglycemia documented by glucose concentration < 3.3 mmol/L (60 mg/dL) or requiring assistance occurs without an easily identifiable reason (skipped meal, excessive physical activity), the daily dose is to be downregulated, with -2 IU/day; Exendin 9-39 will be infused intravenously at doses of 600 pM/kg • min. This will only be during one of the visit for the healthy lean controls and the T2DM group, and during two visits in the group with obesity planned for gastric bypass surgery
Intervention MeSH terms: Insulin Glargine; Liraglutide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)