Combined effects of SGLT2 inhibition and GLP-1 receptor agonism on food intake, body weight and central satiety and reward circuits in obese T2DM patients

Phase 4

Completed

• Conditions: obesitas; 'diabetes'; 'Obesity'; 'overweight'; 'Type 2 Diabetes Mellitus'; 10018424; 10007963

• Registration Number: NL-OMON48777
• Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 64

Inclusion Criteria

For all 4 study groups:
- Age 18-75 years
- BMI 25*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
- Both genders; for women: post menopausal (excluding possible menstruation cycle effects)

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) < 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Differences in neuronal activity in the central reward and satiety circuits in<br /><br>response food related stimuli by BOLD fMRI signal compared to baseline and 16<br /><br>weeks of treatment between the exenatide+dapagliflozine, exenatide + placebo,<br /><br>dapagliflozin+placebo and double placebo groups </p><br>