Study to investigate the effect of dapagliflozin treatment on nocturnal substrate oxidation in overweight and obese subjects with a disrupted glucose homeostasis
Conditions
Sponsors
School of Nutrition and Translational research in Metabolism (NUTRIM), Maastricht University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated informed consent prior to any study specific procedures. 2. Males aged = 40 and = 75 years and post-menopausal women (defined as at least 1 year post cessation of menses) aged = 50 and = 75 years 3. Body mass index (BMI) = 27 and = 38 kg/m2. 4. Sedentary lifestyle (not more than 2 hours of vigorous exercise per week). 5. Stable dietary habits. 6. Impaired glucose homeostasis based on one or a combination of the following criteria: - Impaired Glucose Tolerance (IGT): plasma glucose values = 7.8 mmol/l and = 11.1 mmol/l 120 minutes after consumption of the glucose drink during the 2h, 3-point OGTT. - Impaired Fasting Glucose (IFG): fasting plasma glucose = 6.1 mmol/l and = 6.9 mmol/l. - Insulin Resistance: glucose clearance rate = 360 ml/kg/min, as calculated by Oral Glucose Insulin Sensitivity 120 (OGIS120) model based on the 2h, 3-point OGTT. - HbA1c = 5.7% and = 6.4%. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1. Clinical diagnosis of Type 1 or 2 Diabetes Mellitus. 2. Active cardiovascular disease 3. Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents. 4. Regular smoking and other regular nicotine use. 5. Anaemia. 6. Uncontrolled hypertension. 7. Clinically significant abnormalities in clinical chemistry or hematology 8. Unstable or rapidly progressing renal disease or estimated Glomeral Filtration Rate (eGFR) 14 drinks per week for women and > 21 drinks per week for men. 14. Known hypersensitivity to dapagliflozin or any of the excipients of the product. 15. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding. 16. Any contraindication for MRI scanning.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to examine the effects of dapagliflozin on nocturnal substrate oxidation in overweight or obese subjects with disrupted glucose homeostasis but without T2D.;Secondary Objective: Secondary objectives are to examine if dapagliflozin changes as compared to placebo: - hepatic glycogen content in the morning and evening - 24h glucose, protein or fat oxidation - 24h plasma glucose, NEFA and total amino acid levels, incl. BCAA levels - 24h plasma insulin and glucagon profiles - muscle mitochondrial function - intrahepatic lipid content and composition - intramyocelluar lipid content and composition, including acetylcarnitine levels in the overnight fasted and late afternoon - muscle glycogen content in the overnight fasted and late afternoon - systolic and diastolic blood pressure in the overnight fasted and late afternoon;Primary end point(s): To investigate if Dapagliflozin improves nocturnal substrate oxidation as measured by respiratory quotient (VCO2/VO2) between placebo and active treatment after 2 week double blind treatment. Nocturnal substrate oxidation will be determined during the sleep- period.;Timepoint(s) of evaluation of this end point: 12 till 14 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): No secondary end points;Timepoint(s) of evaluation of this end point: No secondary end points | — |
Countries
Netherlands
Contacts
Public ContactProject leader
Maastricht University
Outcome results
None listed