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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02695810
• Other study ID #: 2015-001552-30
• Status: Completed
• Phase: Phase 2
• Start date: February 24, 2016
• Est. completion date: January 13, 2019

Study information

• Verified date: October 2019
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 13, 2019
• Est. primary completion date: September 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Obesity
• Prediabetic State

Intervention

Drug:
• Dapagliflozin
10 mg per day as monotherapy for 13 weeks
• Metformin
2 x 850 mg per day as monotherapy for 13 weeks

Behavioral:
• Exercise
Interval training, 5 times per week, 30 min per session

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center A/S	Gentofte

Sponsors (5)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	AstraZeneca, Bayer, Rigshospitalet, Denmark, The Novo Nordic Foundation

Country where clinical trial is conducted

Denmark, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring		Change from baseline to 13 weeks and 26 weeks
Secondary	Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA)		Change from baseline to 13 weeks and 26 weeks
Secondary	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
Secondary	HbA1c		Change from baseline to 13 weeks and 26 weeks
Secondary	Glucose concentrations during OGTT		Change from baseline to 13 weeks and 26 weeks
Secondary	Insulin secretion as assessed by the insulinogenic index		Change from baseline to 13 weeks and 26 weeks
Secondary	Insulin sensitivity as assessed by the insulin sensitivity index		Change from baseline to 13 weeks and 26 weeks
Secondary	Body weight (kg)		Change from baseline to 13 weeks and 26 weeks
Secondary	Body fat (%) as assessed by DEXA scan		Change from baseline to 13 weeks and 26 weeks
Secondary	Cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2 max)		Change from baseline to 13 weeks and 26 weeks
Secondary	Respiratory exchange ratio (RER) as assessed by indirect calorimetry		Change from baseline to 13 weeks and 26 weeks
Secondary	Basal metabolic rate (BMR) as assessed by indirect calorimetry		Change from baseline to 13 weeks and 26 weeks
Secondary	Time spent sedentary and in moderate-to-vigorous physical activity intensity as assessed by accelerometer		Change from baseline to 13 weeks and 26 weeks
Secondary	Systolic and diastolic blood pressure		Change from baseline to 13 weeks and 26 weeks
Secondary	Plasma lipids		Change from baseline to 13 weeks and 26 weeks
Secondary	Number of self-reported adverse events and side effects		Change from baseline to 13 weeks and 26 weeks
Secondary	Self-rated health and quality of life as assessed by questionnaire		Change from baseline to 13 weeks and 26 weeks
Secondary	Sleep habits as assessed by questionnaire		Change from baseline to 13 weeks and 26 weeks
Secondary	Dietary intake as assessed by a food diary		Change from baseline to 13 weeks and 26 weeks
Secondary	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
Secondary	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

External Links

•   Steno Diabetes Center