Obesity, Prediabetic State
Conditions
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.
Interventions
DRUGDapagliflozin
10 mg per day as monotherapy for 13 weeks
DRUGMetformin
2 x 850 mg per day as monotherapy for 13 weeks
BEHAVIORALExercise
Interval training, 5 times per week, 30 min per session
Sponsors
The Novo Nordic Foundation
Rigshospitalet, Denmark
AstraZeneca
Bayer
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring | Change from baseline to 13 weeks and 26 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA) | 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 |
| Basal metabolic rate (BMR) as assessed by indirect calorimetry | Change from baseline to 13 weeks and 26 weeks |
Countries
Denmark
Outcome results
None listed