obesitas 'diabetes' 'Obesity' 'overweight' 'Type 2 Diabetes Mellitus'
Conditions
Interventions
Subjects will be randomized in one of the following arms:
1) SGLT2 inhibitor dapagliflozin 10 mg/day in combination with placebo GLP-1
receptor agonist exenatide twice daily,
2) GLP-1 receptor agoni
brain
GLP1 RA
SGLTi
weight
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: For all 4 study groups: - Age 18-75 years - BMI 25*40 kg/m2 - Stable bodyweight ( 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 - Both genders; for women: post menopausal (excluding possible menstruation cycle effects)
Exclusion criteria
Exclusion criteria: For all 4 study groups: - GLP-1 based therapies, dipeptidyl peptidase (DPP)-4, thiazolidinediones or insulin within 3 months before screening - Weight-lowering agents within 3 months before screening. - Congestive heart failure (NYHA II-IV) - Estimated Glomerular Filtration Rate (eGFR) 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 - Individuals who have previously completed or withdrawn from this study or any other study investigating GLP-1 receptor agonist or dipeptidyl peptidase (DPP)-4 within 6 months - Visual disability, not correctable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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Differences in neuronal activity in the central reward and satiety circuits in response food related stimuli by BOLD fMRI signal compared to baseline and 16 weeks of treatment between the exenatide+dapagliflozine, exenatide + placebo, dapagliflozin+placebo and double placebo groups | — |
Secondary
| Measure | Time frame |
|---|---|
| * Differences in neuronal activity in the central reward and satiety circuits in response food related stimuli by BOLD fMRI signal compared to baseline and 1.5 weeks of treatment and 1.5 and 16 weeks of treatment between the exenatide+dapagliflozine, exenatide + placebo, dapagliflozin+placebo and double placebo groups * feeding behaviour, measured by quantitative and qualitative changes in food choice, during an ad libitum lunch buffet compared between the groups ( at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) * difference in self reported hunger, satiety and ful;ness by visual analogue scale *difference in resting energy expenditure measured by indirect calorimetry measurements between the groups (at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) * Change in bodyweight (kg) and body mass index (kg/m2) between the groups (at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) * Difference in bodycomposition measured by bio electrical impedance analysis and other body measurments such as waist and hip circumference between the 4 groups (at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) *difference in resting brain activity by fMRI; resting state measurements * effect on cardiovasculair autonomic balance by cardiovasculair reflex tests with finger plethysmography (Nexfin) (bloodpressure, hartfrequency, ECG). * arterial stiffness: Pulse Wave Analysis (PWA) will be assessed using the SphygmoCor® System (Atcor Medical, West Ryde, Australia), a non-invasive system using applanation tonometry * renal measurements by 24 urine ; glucose excretion (0-1,5, 0-16, 1,5-16 ), creatinine clearance (0-1,5, 0-16, 1,5-16 weeks ), tubulair function ; sodium excretion and urinary pH (0-1,5, 0-16, 1,5-16 weeks), renal damage markers albumin/creatinin ratio (0-1,5, 0-16, 1,5-16weeks ) * Change in the plasma/serum biomarkers of metabolism, liver function, estimated renal function (eG | — |
Countries
The Netherlands
Outcome results
None listed