The PRE-D Trial: Effect of Dapagliflozin, Metformin and Physical Activity in Pre-diabetes
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dapagliflozin Dapagliflozin, 10 mg per day |
Drug: Dapagliflozin
10 mg per day as monotherapy for 13 weeks
Other Names:
|
| Active Comparator: Metformin Metformin, 2 x 850 mg per day |
Drug: Metformin
2 x 850 mg per day as monotherapy for 13 weeks
Other Names:
|
| Active Comparator: Exercise Exercise, interval training |
Behavioral: Exercise
Interval training, 5 times per week, 30 min per session
|
| No Intervention: Control No intervention |
Outcome Measures
Primary Outcome Measures
- Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring [Change from baseline to 13 weeks and 26 weeks]
Secondary Outcome Measures
- Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA) [Change from baseline to 13 weeks and 26 weeks]
- 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) [Change from baseline to 13 weeks and 26 weeks]
- HbA1c [Change from baseline to 13 weeks and 26 weeks]
- Glucose concentrations during OGTT [Change from baseline to 13 weeks and 26 weeks]
- Insulin secretion as assessed by the insulinogenic index [Change from baseline to 13 weeks and 26 weeks]
- Insulin sensitivity as assessed by the insulin sensitivity index [Change from baseline to 13 weeks and 26 weeks]
- Body weight (kg) [Change from baseline to 13 weeks and 26 weeks]
- Body fat (%) as assessed by DEXA scan [Change from baseline to 13 weeks and 26 weeks]
- Cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2 max) [Change from baseline to 13 weeks and 26 weeks]
- Respiratory exchange ratio (RER) as assessed by indirect calorimetry [Change from baseline to 13 weeks and 26 weeks]
- Basal metabolic rate (BMR) as assessed by indirect calorimetry [Change from baseline to 13 weeks and 26 weeks]
- Time spent sedentary and in moderate-to-vigorous physical activity intensity as assessed by accelerometer [Change from baseline to 13 weeks and 26 weeks]
- Systolic and diastolic blood pressure [Change from baseline to 13 weeks and 26 weeks]
- Plasma lipids [Change from baseline to 13 weeks and 26 weeks]
- Number of self-reported adverse events and side effects [Change from baseline to 13 weeks and 26 weeks]
- Self-rated health and quality of life as assessed by questionnaire [Change from baseline to 13 weeks and 26 weeks]
- Sleep habits as assessed by questionnaire [Change from baseline to 13 weeks and 26 weeks]
- Dietary intake as assessed by a food diary [Change from baseline to 13 weeks and 26 weeks]
- Adherence to the different interventions as assessed by number of tablets returned or number of training passes completed [Change from baseline to 13 weeks and 26 weeks]
- Responsiveness to interventions in individuals with different glucose tolerance status (impaired fasting glycaemia vs. impaired glucose tolerance) [Change from baseline to 13 weeks and 26 weeks]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Steno Diabetes Center A/S | Gentofte | Denmark | 2820 |
Sponsors and Collaborators
- Steno Diabetes Center Copenhagen
- The Novo Nordic Foundation
- Rigshospitalet, Denmark
- AstraZeneca
- Bayer
Investigators
- Principal Investigator: Marit E Jørgensen, PhD, Steno Diabetes Center Copenhagen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Faerch K, Hulmán 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. Review.
- Færch K, Vistisen D, Johansen NB, Jørgensen ME. Cardiovascular risk stratification and management in pre-diabetes. Curr Diab Rep. 2014 Jun;14(6):493. doi: 10.1007/s11892-014-0493-1. Review.
- Perreault L, Færch 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. Review.
- 2015-001552-30