NCT02695810

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2016

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2016

Completed
15 days until next milestone

Study Start

First participant enrolled

February 24, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 1, 2016

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 20, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 13, 2019

Completed
Last Updated

October 7, 2019

Status Verified

October 1, 2019

Enrollment Period

2.6 years

First QC Date

February 9, 2016

Last Update Submit

October 4, 2019

Conditions

Prediabetic StateObesity

Outcome Measures

Primary Outcomes (1)

  • Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring

    Change from baseline to 13 weeks and 26 weeks

Secondary Outcomes (20)

  • 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

  • +15 more secondary outcomes

Study Arms (4)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin, 10 mg per day

Drug: Dapagliflozin

Metformin

ACTIVE COMPARATOR

Metformin, 2 x 850 mg per day

Drug: Metformin

Exercise

ACTIVE COMPARATOR

Exercise, interval training

Behavioral: Exercise

Control

NO INTERVENTION

No intervention

Interventions

DapagliflozinDRUG

10 mg per day as monotherapy for 13 weeks

Also known as: Forxiga, AstraZeneca
Dapagliflozin
MetforminDRUG

2 x 850 mg per day as monotherapy for 13 weeks

Also known as: Aurobindo, Orion Pharma
Metformin
ExerciseBEHAVIORAL

Interval training, 5 times per week, 30 min per session

Exercise

Eligibility Criteria

Age30 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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;
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Steno Diabetes Center A/S

Gentofte Municipality, 2820, Denmark

Location

Related Publications (6)

  • 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.

    PMID: 24342268BACKGROUND

  • 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.

    PMID: 25877695BACKGROUND

  • 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.

    PMID: 24743942BACKGROUND

  • 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.

    PMID: 33705389DERIVED

  • 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.

    PMID: 33064182DERIVED

  • 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.

    PMID: 28592573DERIVED

Related Links

MeSH Terms

Conditions

Prediabetic StateObesity

Interventions

dapagliflozinMetforminExercise

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic ChemicalsMotor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Marit E Jørgensen, PhD

    Steno Diabetes Center Copenhagen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Researcher

Study Record Dates

First Submitted

February 9, 2016

First Posted

March 1, 2016

Study Start

February 24, 2016

Primary Completion

September 20, 2018

Study Completion

January 13, 2019

Last Updated

October 7, 2019

Record last verified: 2019-10

Data Sharing

IPD Sharing
Will not share

Locations

DK(1)