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

Launched by AMSTERDAM UMC, LOCATION VUMC · Nov 27, 2017

Keywords

ClinConnect Summary

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...

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Eligibility 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