Back to resultsThe PRE-D Trial: Effect of Dapagliflozin, Metformin and Physical Activity in Pre-diabetes
Primary Purpose
Prediabetic State, Obesity
Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Dapagliflozin
Metformin
Exercise
Sponsored by
About this trial
This is an interventional prevention trial for Prediabetic State
Eligibility Criteria
Inclusion Criteria:
- HbA1c: from ≥5.7% (39 mmol/mol) to ≤6.4% (47 mmol/mol)
- Age: from ≥30 to ≤70 years of age
- BMI ≥25 kg/m2
Exclusion Criteria:
- Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, gastrointestinal or psychiatric disease; diabetes or other endocrine disease; immunosuppression;
- Current treatment with hormones which affect glucose metabolism;
- Current treatment with loop diuretics or thiazolidinediones;
- Current treatment with beta blockers or peroral steroids;
- Bariatric surgery within the past 2 years;
- Impaired renal function defined as an estimated GFR<60 ml/min/1.73m2;
- Neurogenic bladder disorders;
- Alcohol/drug abuse or in treatment with disulfiram (Antabus) at time of inclusion;
- Pregnant or lactating women;
- Fertile women not using birth control agents including oral contraceptives, gestagen injection, subdermal implants, hormonal vaginal ring, transdermal application, or intra-uterine devices;
- Allergic to one or more of the medications used in the study;
- Concomitant participation in other intervention study;
- Unable to understand the informed consent and the study procedures.
Sites / Locations
- Steno Diabetes Center A/S
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Active Comparator
No Intervention
Arm Label
Dapagliflozin
Metformin
Exercise
Control
Arm Description
Dapagliflozin, 10 mg per day
Metformin, 2 x 850 mg per day
Exercise, interval training
No intervention
Outcomes
Primary Outcome Measures
Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring
Secondary Outcome Measures
Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA)
Daily time spent above different glucose concentrations ( e.g. >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L)
HbA1c
Glucose concentrations during OGTT
Insulin secretion as assessed by the insulinogenic index
Insulin sensitivity as assessed by the insulin sensitivity index
Body weight (kg)
Body fat (%) as assessed by DEXA scan
Cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2 max)
Respiratory exchange ratio (RER) as assessed by indirect calorimetry
Basal metabolic rate (BMR) as assessed by indirect calorimetry
Time spent sedentary and in moderate-to-vigorous physical activity intensity as assessed by accelerometer
Systolic and diastolic blood pressure
Plasma lipids
Number of self-reported adverse events and side effects
Self-rated health and quality of life as assessed by questionnaire
Sleep habits as assessed by questionnaire
Dietary intake as assessed by a food diary
Adherence to the different interventions as assessed by number of tablets returned or number of training passes completed
Responsiveness to interventions in individuals with different glucose tolerance status (impaired fasting glycaemia vs. impaired glucose tolerance)
Full Information
NCT ID
NCT02695810
First Posted
February 9, 2016
Last Updated
October 4, 2019
Sponsor
Steno Diabetes Center Copenhagen
Collaborators
The Novo Nordic Foundation, Rigshospitalet, Denmark, AstraZeneca, Bayer
1. Study Identification
Unique Protocol Identification Number
NCT02695810
Brief Title
The PRE-D Trial: Effect of Dapagliflozin, Metformin and Physical Activity in Pre-diabetes
Official Title
Effect of Dapagliflozin, Metformin and Physical Activity on Glucose Variability, Body Composition and Cardiovascular Risk in Pre-diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
February 24, 2016 (Actual)
Primary Completion Date
September 20, 2018 (Actual)
Study Completion Date
January 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Steno Diabetes Center Copenhagen
Collaborators
The Novo Nordic Foundation, Rigshospitalet, Denmark, AstraZeneca, Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The overall objective is to compare the short-term (3 months) effectiveness of three glucose-lowering interventions (dapagliflozin, metformin and physical activity) on glucose variability, body composition, and cardiometabolic risk factors in overweight or obese individuals with pre-diabetes (HbA1c 5.7-6.4% / 39-47 mmol/mol).
Detailed Description
Different medical therapies and lifestyle modification for the prevention of type 2 diabetes have yet to be compared head-to-head in individuals with pre-diabetes. This research project will compare different glucose-lowering interventions in overweight and obese individuals with HbA1c levels in the pre-diabetic range.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prediabetic State, Obesity
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dapagliflozin
Arm Type
Experimental
Arm Description
Dapagliflozin, 10 mg per day
Arm Title
Metformin
Arm Type
Active Comparator
Arm Description
Metformin, 2 x 850 mg per day
Arm Title
Exercise
Arm Type
Active Comparator
Arm Description
Exercise, interval training
Arm Title
Control
Arm Type
No Intervention
Arm Description
No intervention
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Other Intervention Name(s)
Forxiga, AstraZeneca
Intervention Description
10 mg per day as monotherapy for 13 weeks
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Aurobindo, Orion Pharma
Intervention Description
2 x 850 mg per day as monotherapy for 13 weeks
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
Interval training, 5 times per week, 30 min per session
Primary Outcome Measure Information:
Title
Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring
Time Frame
Change from baseline to 13 weeks and 26 weeks
Secondary Outcome Measure Information:
Title
Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA)
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Daily time spent above different glucose concentrations ( e.g. >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L)
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
HbA1c
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Glucose concentrations during OGTT
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Insulin secretion as assessed by the insulinogenic index
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Insulin sensitivity as assessed by the insulin sensitivity index
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Body weight (kg)
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Body fat (%) as assessed by DEXA scan
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2 max)
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Respiratory exchange ratio (RER) as assessed by indirect calorimetry
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Basal metabolic rate (BMR) as assessed by indirect calorimetry
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Time spent sedentary and in moderate-to-vigorous physical activity intensity as assessed by accelerometer
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Systolic and diastolic blood pressure
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Plasma lipids
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Number of self-reported adverse events and side effects
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Self-rated health and quality of life as assessed by questionnaire
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Sleep habits as assessed by questionnaire
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Dietary intake as assessed by a food diary
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Adherence to the different interventions as assessed by number of tablets returned or number of training passes completed
Time Frame
Change from baseline to 13 weeks and 26 weeks
Title
Responsiveness to interventions in individuals with different glucose tolerance status (impaired fasting glycaemia vs. impaired glucose tolerance)
Time Frame
Change from baseline to 13 weeks and 26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
HbA1c: from ≥5.7% (39 mmol/mol) to ≤6.4% (47 mmol/mol)
Age: from ≥30 to ≤70 years of age
BMI ≥25 kg/m2
Exclusion Criteria:
Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, gastrointestinal or psychiatric disease; diabetes or other endocrine disease; immunosuppression;
Current treatment with hormones which affect glucose metabolism;
Current treatment with loop diuretics or thiazolidinediones;
Current treatment with beta blockers or peroral steroids;
Bariatric surgery within the past 2 years;
Impaired renal function defined as an estimated GFR<60 ml/min/1.73m2;
Neurogenic bladder disorders;
Alcohol/drug abuse or in treatment with disulfiram (Antabus) at time of inclusion;
Pregnant or lactating women;
Fertile women not using birth control agents including oral contraceptives, gestagen injection, subdermal implants, hormonal vaginal ring, transdermal application, or intra-uterine devices;
Allergic to one or more of the medications used in the study;
Concomitant participation in other intervention study;
Unable to understand the informed consent and the study procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marit E Jørgensen, PhD
Organizational Affiliation
Steno Diabetes Center Copenhagen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Steno Diabetes Center A/S
City
Gentofte
ZIP/Postal Code
2820
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24342268
Citation
Perreault L, Faerch K. Approaching pre-diabetes. J Diabetes Complications. 2014 Mar-Apr;28(2):226-33. doi: 10.1016/j.jdiacomp.2013.10.008. Epub 2013 Oct 28.
Results Reference
background
PubMed Identifier
25877695
Citation
Faerch K, Hulman A, Solomon TP. Heterogeneity of Pre-diabetes and Type 2 Diabetes: Implications for Prediction, Prevention and Treatment Responsiveness. Curr Diabetes Rev. 2016;12(1):30-41. doi: 10.2174/1573399811666150416122903.
Results Reference
background
PubMed Identifier
24743942
Citation
Faerch K, Vistisen D, Johansen NB, Jorgensen ME. Cardiovascular risk stratification and management in pre-diabetes. Curr Diab Rep. 2014 Jun;14(6):493. doi: 10.1007/s11892-014-0493-1.
Results Reference
background
PubMed Identifier
33705389
Citation
Hulman A, Foreman YD, Brouwers MCGJ, Kroon AA, Reesink KD, Dagnelie PC, van der Kallen CJH, Greevenbroek MMJV, Faerch K, Vistisen D, Jorgensen ME, Stehouwer CDA, Witte DR. Towards precision medicine in diabetes? A critical review of glucotypes. PLoS Biol. 2021 Mar 11;19(3):e3000890. doi: 10.1371/journal.pbio.3000890. eCollection 2021 Mar.
Results Reference
derived
PubMed Identifier
33064182
Citation
Faerch K, Blond MB, Bruhn L, Amadid H, Vistisen D, Clemmensen KKB, Vaino CTR, Pedersen C, Tvermosegaard M, Dejgaard TF, Karstoft K, Ried-Larsen M, Persson F, Jorgensen ME. The effects of dapagliflozin, metformin or exercise on glycaemic variability in overweight or obese individuals with prediabetes (the PRE-D Trial): a multi-arm, randomised, controlled trial. Diabetologia. 2021 Jan;64(1):42-55. doi: 10.1007/s00125-020-05306-1. Epub 2020 Oct 16.
Results Reference
derived
PubMed Identifier
28592573
Citation
Faerch K, Amadid H, Nielsen LB, Ried-Larsen M, Karstoft K, Persson F, Jorgensen ME. Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial). BMJ Open. 2017 Jun 6;7(5):e013802. doi: 10.1136/bmjopen-2016-013802.
Results Reference
derived
Links:
URL
http://steno.dk/
Description
Steno Diabetes Center
Learn more about this trial
The PRE-D Trial: Effect of Dapagliflozin, Metformin and Physical Activity in Pre-diabetes
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