DECREASE

CompletedPhase 4

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

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

Lead sponsor

Amsterdam UMC, location VUmc

Asset

Exenatide

GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criteria

•BMI 27-40•HbA1c 7-10%

Primary endpoint

•Differences in neuronal activity in the central reward

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03361098

Org study IDDC2017DECREASE01

Timeline

Milestones

Study start2017-09-18actual

Study first posted2017-12-04actual

Primary completion2019-11-25actual

Study completion2020-03-25actual

Last update posted2021-06-11actual

Assets

Investigational agents

Exenatide

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

Maximum age75 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (18)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Cardiometabolic biomarkers

Other clinical outcomes

Weight & body composition

Safety / tolerability / PK

Renal / kidney

Patient-reported / QoL

Weight & body composition

2 endpoints

Secondary/protocol endpoint

Change in bodyweight (kg) and body mass index (kg/m2)

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Difference in bodycomposition measured by bio electrical impedance analysis and waist and hip circumference measurements (cm)

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, improvement

componentsTotal fat mass, Waist circumference, change

Renal / kidney

1 endpoint

Secondary/protocol endpoint

Renal measurements collecting 24 hour urine

Time frame:at baseline, after 10 days and after 16 weeks

descriptive

Cardiometabolic biomarkers

3 endpoints

Secondary/protocol endpoint/low confidence

Effect on cardiovascular autonomic balance by cardiovascular reflex test with finger plethysmography (Nexfin)

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, improvement

Secondary/protocol endpoint

Arterial stiffness: Pulse Wave analysis

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, improvement

Other/protocol endpoint/low confidence

Exploratory objective: measurement of hormones

Time frame:16 weeks

Leptin, change

descriptive

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Self-reported hunger

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Other/protocol endpoint

Safety outcomes; Adverse events

Time frame:+/- 21 weeks

Treatment-emergent AEs (any)

event count, event

Other/protocol endpoint

Safety outcome; vital signs

Time frame:16 weeks

descriptive

Other clinical outcomes

3 endpoints

Primary/protocol endpoint

Differences in neuronal activity in the central reward and satiety circuits in response to food-related stimuli by BOLD fMRI signal

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Feeding behaviour; ad libitum lunch buffet

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, improvement

Secondary/protocol endpoint

Feeding behaviour; ad libitum lunch buffet

Time frame:at baseline, after 10 days and after 16 weeks

descriptive

Other (unclassified)

6 endpoints

Secondary/protocol endpoint/low confidence

Differences in neuronal activity in the central reward and satiety circuits in response to food-related stimuli by BOLD fMRI signal

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Difference in resting energy expenditure measured by indirect calorimetry measurements

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Difference in resting brain activity by fMRI resting state measurements

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Laboratory parameters

Time frame:at baseline, after 10 days and after 16 weeks

change from baseline, descriptive

Other/protocol endpoint/low confidence

Exploratory objective: Cerebral perfusion assessed by Arterial Spin Labeling

Time frame:16 weeks

change from baseline, descriptive

Other/protocol endpoint/low confidence

Exploratory: Microbiome

Time frame:Baseline and after 16 weeks

descriptive

Publications (21)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes.
The Journal of clinical endocrinology and metabolism2022 May 17PMID35134184doi:10.1210/clinem/dgac043via clinicaltrials gov reference derived + pubmed nct search
Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial.
Cardiovascular diabetology2022 Apr 28PMID35484607doi:10.1186/s12933-022-01492-xvia clinicaltrials gov reference derived + pubmed nct search
GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes.
Nature reviews. Nephrology2017 Oct (month)PMID28869249doi:10.1038/nrneph.2017.123via CT.gov background
Dapagliflozin once daily plus exenatide once weekly in obese adults without diabetes: Sustained reductions in body weight, glycaemia and blood pressure over 1 year.
Diabetes, obesity & metabolism2017 Sep (month)PMID28345814doi:10.1111/dom.12954via CT.gov background
Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial.
The lancet. Diabetes & endocrinology2016 Dec (month)PMID27651331doi:10.1016/S2213-8587(16)30267-4via CT.gov background
Alterations in white matter volume and integrity in obesity and type 2 diabetes.
Metabolic brain disease2016 Jun (month)PMID26815786doi:10.1007/s11011-016-9792-3via CT.gov background
Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients.
The Journal of clinical endocrinology and metabolism2016 May (month)PMID26672638doi:10.1210/jc.2015-3291via CT.gov background
Endogenous GLP1 and GLP1 analogue alter CNS responses to palatable food consumption.
The Journal of endocrinology2016 Apr (month)PMID26769912doi:10.1530/JOE-15-0461via CT.gov background
Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition.
Diabetes, obesity & metabolism2016 Feb (month)PMID26403227doi:10.1111/dom.12578via CT.gov background
Endogenous GLP-1 mediates postprandial reductions in activation in central reward and satiety areas in patients with type 2 diabetes.
Diabetologia2015 Dec (month)PMID26385462doi:10.1007/s00125-015-3754-xvia CT.gov background
Emotional eating is associated with increased brain responses to food-cues and reduced sensitivity to GLP-1 receptor activation.
Obesity (Silver Spring, Md.)2015 Oct (month)PMID26331843doi:10.1002/oby.21200via CT.gov background
Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition.
Diabetes care2015 Sep (month)PMID26180105doi:10.2337/dc15-0355via CT.gov background
Brain reward-system activation in response to anticipation and consumption of palatable food is altered by glucagon-like peptide-1 receptor activation in humans.
Diabetes, obesity & metabolism2015 Sep (month)PMID26094857doi:10.1111/dom.12506via CT.gov background
Pleiotropic effects of type 2 diabetes management strategies on renal risk factors.
The lancet. Diabetes & endocrinology2015 May (month)PMID25943756doi:10.1016/S2213-8587(15)00030-3via CT.gov background
GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans.
Diabetes2014 Dec (month)PMID25071023doi:10.2337/db14-0849via CT.gov background
Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS.
The Journal of endocrinology2014 Apr (month)PMID24323912doi:10.1530/JOE-13-0414via CT.gov background
Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients.
The Journal of clinical investigation2014 Feb (month)PMID24463454doi:10.1172/JCI72227via CT.gov background
Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats.
Obesity (Silver Spring, Md.)2012 Aug (month)PMID22402735doi:10.1038/oby.2012.59via CT.gov background
fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program.
NeuroImage2012 Feb 1PMID22332246doi:10.1016/j.neuroimage.2011.10.071via CT.gov background
Processing of food pictures: influence of hunger, gender and calorie content.
Brain research2010 Sep 2PMID20423700doi:10.1016/j.brainres.2010.04.030via CT.gov background
Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals.
NeuroImage2007 Aug 15PMID17566768doi:10.1016/j.neuroimage.2007.05.008via CT.gov background

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.