DECREASE: Dapagliflozin Plus Exenatide on Central REgulation of Appetite in diabeteS typE 2

• Status: Completed
• Trial end date: 2020-03-25
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VU University Medical Center
• Collaborator: AstraZeneca
• Treatments: Dapagliflozin; Exenatide; Glucagon; Glucagon-Like Peptide 1; Sodium-Glucose Transporter 2 Inhibitors

Criteria

Inclusion Criteria:

• Age 18-75 years

• BMI 27-40 kg/m2

• Stable bodyweight (<5% reported change during the previous 3 months).

• Diagnosed with T2DM > 3 months prior to screening

• Treatment with metformin and/or sulphonylurea at a stable dose for at least 3 months.

• HbA1c 7.0-10% for patients treated with metformin

• HbA1c 7.5-10% for patients treated with metformin and/ or sulphonylurea

• For women: post menopausal (excluding possible menstruation cycle effects)

Exclusion Criteria:

• GLP-1 based therapies, DDP-4 inhibitors, SGLT-2 inhibitors, thiazolidinediones or insulin within 3 months before screening

• Weight-lowering agents within 3 months before screening.

• Congestive heart failure (NYHA II-IV)

• Chronic renal failure (glomerular filtration rate < 45 mL/min/1.73m2 per Modification of Diet in Renal Disease (MDRD))

• Liver disease

• History of gastrointestinal disorders (including gastroparese, pancreatitis and cholelithiasis)

• Patients with MEN2 syndrome or history or family history of medullary thyroid carcinoma

• Neurological illness

• Malignancy (except for basal cell carcinoma)

• History of major heart disease

• History of major renal disease

• Pregnancy or breast feeding

• Implantable devices

• Substance abuse

• Addiction

• Alcohol abuse (defined as: for men > 21 units/week, for women >14 units/week)

• Smoking/ nicotine abuse (defined as: daily smoking / a daily use of nicotine)

• Contra-indication for MRI, such as claustrophobia or pacemaker

• psychiatric illnesses; mood disorders, eating disorders, anxiety disorders, schizophrenia and other psychotic disorders, dissociative disorders, somatoform disorders, delirium, dementia and other cognitive disorders

• Chronic use of centrally acting agents or glucocorticoids within 2 weeks immediately prior to screening

• Use of cytostatic or immune modulatory agents

• History of allergy for exenatide or other GLP-1 RA

• Participation in other studies

• Individuals who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

• Individuals who are investigator site personnel, directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

• Individuals who have previously completed or withdrawn from this study or any other study investigating GLP-1 receptor agonist or dipeptidyl peptidase (DPP)-4 within 6 months

• Visual disability, not correctable with glasses or contact lens

• Individuals who, in the opinion of the investigator, are unsuitable in any other way to participate in this study

• Poor commandment of the Dutch language or any (mental) disorder that precludes full understanding the purpose, instruction and hence participation in the study

• Further exclusion criteria will be in compliance with the EMeA SPC of exenatide and dapagliflozin