PMID- 28132008
OWN - NLM
STAT- MEDLINE
DCOM- 20171213
LR  - 20210504
IS  - 2044-6055 (Electronic)
IS  - 2044-6055 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jan 27
TI  - Compensatory changes in energy balance during dapagliflozin treatment in type 2 
      diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over 
      trial (ENERGIZE)-study protocol.
PG  - e013539
LID - 10.1136/bmjopen-2016-013539 [doi]
LID - e013539
AB  - INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective 
      blood-glucose-lowering medications with beneficial effects on body weight in 
      patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is 
      less than that predicted from quantified glycosuria, suggesting a compensatory 
      increase in energy intake or a decrease in energy expenditure. Studies using 
      dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is 
      due to loss of adipose tissue, but organ-specific changes in fat content (eg, 
      liver, skeletal muscle) have not been determined. In this randomised, 
      double-blind, placebo-controlled crossover study, we aim to study the 
      compensatory changes in energy intake, eating behaviour and energy expenditure 
      accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to 
      quantify changes in fat distribution using MRI, in liver fat using proton 
      magnetic resonance spectroscopy ((1)H-MRS) and in central nervous system (CNS) 
      responses to food images using blood oxygen level dependent (BOLD) functional MRI 
      (fMRI). METHODS AND ANALYSIS: This outpatient study will evaluate the effect of 
      dapagliflozin (10 mg), compared with placebo, on food intake and energy 
      expenditure at 7 days and 12 weeks. 52 patients with T2DM will be randomised to 
      dapagliflozin or placebo for short-term and long-term trial interventions in a 
      within participants, crossover design. The primary outcome is the difference in 
      energy intake during a test meal between dapagliflozin and placebo. Intake data 
      are collected automatically using a customised programme operating a universal 
      eating monitor (UEM). Secondary outcomes include (1) measures of appetite 
      regulation including rate of eating, satiety quotient, appetite ratings (between 
      and within meals), changes in CNS responses to food images measured using 
      BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition 
      including changes in liver fat and abdominal visceral adipose tissue (VAT) and 
      subcutaneous adipose tissue (SAT). ETHICAL APPROVAL: This study has been approved 
      by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is 
      conducted in accordance with the Declaration of Helsinki and the Good Clinical 
      Practice (GCP). TRIAL REGISTRATION NUMBER: ISRCTN14818531. EUDRACT number 
      2013-004264-60.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/.
FAU - Rajeev, Surya Panicker
AU  - Rajeev SP
AD  - Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
AD  - Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree 
      University Hospital NHS Foundation Trust, Liverpool, UK.
FAU - Sprung, Victoria S
AU  - Sprung VS
AD  - Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree 
      University Hospital NHS Foundation Trust, Liverpool, UK.
AD  - Department of Musculoskeletal Biology II, Institute of Ageing and Chronic 
      Disease, University of Liverpool, Liverpool, UK.
FAU - Roberts, Carl
AU  - Roberts C
AD  - Department of Psychological Sciences, Institute of Psychology, Health and 
      Society, University of Liverpool, Liverpool, UK.
FAU - Harrold, Jo A
AU  - Harrold JA
AD  - Department of Psychological Sciences, Institute of Psychology, Health and 
      Society, University of Liverpool, Liverpool, UK.
FAU - Halford, Jason C G
AU  - Halford JC
AD  - Department of Psychological Sciences, Institute of Psychology, Health and 
      Society, University of Liverpool, Liverpool, UK.
FAU - Stancak, Andrej
AU  - Stancak A
AD  - Department of Psychological Sciences, Institute of Psychology, Health and 
      Society, University of Liverpool, Liverpool, UK.
FAU - Boyland, Emma J
AU  - Boyland EJ
AD  - Department of Psychological Sciences, Institute of Psychology, Health and 
      Society, University of Liverpool, Liverpool, UK.
FAU - Kemp, Graham J
AU  - Kemp GJ
AD  - Department of Musculoskeletal Biology II, Institute of Ageing and Chronic 
      Disease, University of Liverpool, Liverpool, UK.
AD  - Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of 
      Liverpool, Liverpool, UK.
FAU - Cuthbertson, Daniel J
AU  - Cuthbertson DJ
AD  - Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree 
      University Hospital NHS Foundation Trust, Liverpool, UK.
AD  - Department of Musculoskeletal Biology II, Institute of Ageing and Chronic 
      Disease, University of Liverpool, Liverpool, UK.
FAU - Wilding, John P H
AU  - Wilding JP
AD  - Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
AD  - Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree 
      University Hospital NHS Foundation Trust, Liverpool, UK.
LA  - eng
SI  - ISRCTN/ISRCTN14818531
SI  - EudraCT/2013-004264-60
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170127
PL  - England
TA  - BMJ Open
JT  - BMJ open
JID - 101552874
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 1ULL0QJ8UC (dapagliflozin)
SB  - IM
MH  - Adipose Tissue/diagnostic imaging/pathology
MH  - Benzhydryl Compounds/*therapeutic use
MH  - Body Composition
MH  - Body Fat Distribution
MH  - Brain/*diagnostic imaging/physiopathology
MH  - Calorimetry, Indirect
MH  - Cross-Over Studies
MH  - Cues
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Eating
MH  - *Energy Metabolism
MH  - Feeding Behavior
MH  - Food
MH  - Functional Neuroimaging
MH  - Glucosides/*therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Intra-Abdominal Fat/*metabolism
MH  - Liver
MH  - Magnetic Resonance Imaging
MH  - Organ Size
MH  - Proton Magnetic Resonance Spectroscopy
PMC - PMC5278268
COIS- JW has acted as a consultant, received institutional grants and given lectures on 
      behalf of pharmaceutical companies developing or marketing medicines used for the 
      treatment of diabetes, specifically AstraZeneca, Boehringer Ingelheim, Janssen 
      Pharmaceuticals, Lilly, Novo Nordisk and Sanofi &Takeda. DJC has competing 
      interests with AstraZeneca, Boehringer Ingelheim, Janssen Pharmaceuticals, Lilly 
      & Novo Nordisk. JCGH has acted as a consultant for Orexigen and Novo Nordisk. 
      Other authors have no competing interests.
EDAT- 2017/01/31 06:00
MHDA- 2017/12/14 06:00
PMCR- 2017/01/27
CRDT- 2017/01/30 06:00
PHST- 2017/01/30 06:00 [entrez]
PHST- 2017/01/31 06:00 [pubmed]
PHST- 2017/12/14 06:00 [medline]
PHST- 2017/01/27 00:00 [pmc-release]
AID - bmjopen-2016-013539 [pii]
AID - 10.1136/bmjopen-2016-013539 [doi]
PST - epublish
SO  - BMJ Open. 2017 Jan 27;7(1):e013539. doi: 10.1136/bmjopen-2016-013539.