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

October 4, 2019 updated by: Kristine Færch, Steno Diabetes Center Copenhagen

Effect of Dapagliflozin, Metformin and Physical Activity on Glucose Variability, Body Composition and Cardiovascular Risk in Pre-diabetes

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Gentofte, Denmark, 2820
        • Steno Diabetes Center A/S

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Control
No intervention
EXPERIMENTAL: Dapagliflozin
Dapagliflozin, 10 mg per day
Drug: Dapagliflozin
10 mg per day as monotherapy for 13 weeks
Other Names:
  • Forxiga, AstraZeneca
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:
  • Aurobindo, Orion Pharma
ACTIVE_COMPARATOR: Exercise
Exercise, interval training
Behavioral: Exercise
Interval training, 5 times per week, 30 min per session

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA)
Time Frame: Change from baseline to 13 weeks and 26 weeks
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)
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
HbA1c
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Glucose concentrations during OGTT
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Insulin secretion as assessed by the insulinogenic index
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Insulin sensitivity as assessed by the insulin sensitivity index
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Body weight (kg)
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Body fat (%) as assessed by DEXA scan
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2 max)
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Respiratory exchange ratio (RER) as assessed by indirect calorimetry
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Basal metabolic rate (BMR) as assessed by indirect calorimetry
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
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
Change from baseline to 13 weeks and 26 weeks
Systolic and diastolic blood pressure
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Plasma lipids
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Number of self-reported adverse events and side effects
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Self-rated health and quality of life as assessed by questionnaire
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Sleep habits as assessed by questionnaire
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks
Dietary intake as assessed by a food diary
Time Frame: Change from baseline to 13 weeks and 26 weeks
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
Time Frame: Change from baseline to 13 weeks and 26 weeks
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)
Time Frame: Change from baseline to 13 weeks and 26 weeks
Change from baseline to 13 weeks and 26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Steno Diabetes Center Copenhagen

Collaborators

Bayer
AstraZeneca
Rigshospitalet, Denmark
The Novo Nordic Foundation

Investigators

  • Principal Investigator: Marit E Jørgensen, PhD, Steno Diabetes Center Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 24, 2016

Primary Completion (ACTUAL)

September 20, 2018

Study Completion (ACTUAL)

January 13, 2019

Study Registration Dates

First Submitted

February 9, 2016

First Submitted That Met QC Criteria

February 24, 2016

First Posted (ESTIMATE)

March 1, 2016

Study Record Updates

Last Update Posted (ACTUAL)

October 7, 2019

Last Update Submitted That Met QC Criteria

October 4, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-001552-30

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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