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

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).

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.

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.