The PRE-D Trial: Effect of Dapagliflozin, Metformin and Physical Activity in Pre-diabetes

Phase 2

Completed

• Conditions: Prediabetic State; Obesity
• Interventions: Drug: Dapagliflozin; Drug: Metformin; Behavioral: Exercise

• Registration Number: NCT02695810
• Lead Sponsor: Steno Diabetes Center Copenhagen

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.

Study Timeline

• Study First Submitted: 2016-02-09
• Study Start: 2016-02-24
• Study First Submitted QC: 2016-02-24
• Study First Posted: 2016-03-01
• Primary Completion: 2018-09-20
• Study Completion: 2019-01-13
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-04
• Last Update Posted: 2019-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin	Dapagliflozin	Dapagliflozin, 10 mg per day
Metformin	Metformin	Metformin, 2 x 850 mg per day
Exercise	Exercise	Exercise, interval training

Primary Outcome Measures

Name	Time	Method
Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring	Change from baseline to 13 weeks and 26 weeks

Secondary Outcome Measures

Name	Time	Method
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
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
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
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
Glucose concentrations during OGTT	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
Systolic and diastolic blood pressure	Change from baseline to 13 weeks and 26 weeks
Sleep habits as assessed by questionnaire	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
Dietary intake as assessed by a food diary	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
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

Trial Locations

Locations (1)

Steno Diabetes Center A/S; 🇩🇰 Gentofte, Denmark