Evaluate the Effects of Dapagliflozin in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This study will make it possible to better understand the mechanisms responsible for the increase in bad cholesterol levels observed in patients with type 2 diabetes treated with Dapagliflozin, an antidiabetic treatment made by Astrazeneca. The information will: reveal what is not working properly make it possible to choose the most appropriate treatments against cholesterol to compensate for this impaired functioning This biomedical research will take place at the University Hospitals of DIJON and NANTES. 28 patients will take part: 20 patients will be given Dapagliflozin and 8 patients will be given the placebo. The study treatment will be randomised: patients will be given either Dapagliflozin or the placebo. The treatment duration is 6 months. Moreover, during the inclusion visit and at the end of the study (6 months after the start of treatment), a kinetics study, to follow the production and elimination of cholesterol, will be conducted. This will involve administering amino acids that have been specifically synthesised for this purpose. Participation in the study will last 6 months and include 4 protocol visits.

Official Title
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Effects of Dapagliflozin on Lipoprotein Kinetics in Patients With Type 2 Diabetes

Conditions
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Type-2 Diabetes, Oral Antidiabetics

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: persons who have provided written consent type 2 diabetes treated with OAD (metformin and/or sulfonylurea and/or glinides and/or acarbose and/or DPPIV inhibitors) Stable treatment for 3 months HbA1c between 7.5% and 10% Age between 30 and 65 years BMI between 25 and 35 kg/m² Triglycerides < 300 mg/dl Half of the patients being treated with statins eGFR > 75 ml/min/1.73 m² at inclusion Exclusion Criteria: persons without national health insurance cover patients treated with Insulin or a GLP-1 agonist Patients under guardianship patients treated with lipid-lowering drugs (except statins for 50% of patients) kidney failure liver failure or abnormal liver function ASAT or ALAT >3 x upper limit of normal total bilirubin >2mg/dl intestinal disease serological evidence of an active liver infection (surface antigen of hepatitis B, hepatitis C antibodies, hepatitis B IgM antibodies) Pregnancy, breastfeeding hypersensitivity to the active substance or to excipients patients with volume depletion, for example due to an acute disease (gastro-intestinal disease) patients treated with loop diuretics or thiazides

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients not treated with statins<br> | Drug: Dapagliflozin<br>* Dapagliflozin 10 mg daily per os<br>Drug: Placebos<br>* Placebo of Dapagliflozin per day per os<br>|
| Experimental: Patients treated with statins<br> | Drug: Dapagliflozin<br>* Dapagliflozin 10 mg daily per os<br>Drug: Placebos<br>* Placebo of Dapagliflozin per day per os<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline the rate of production of VLDL Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the rate of production of IDL Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the rate of production of LDL Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the rate of production of HDL Apo A1 |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the Fractional Catabolic Rate of VLDL1 Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the Fractional Catabolic Rate of VLDL2 Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the Fractional Catabolic Rate of IDL Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the Fractional Catabolic Rate of LDL Apo B |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 | 
| Change from baseline the Fractional Catabolic Rate of HDL 'Apo A1 |  | 15 days before treatment initiation, Day 0, Day 90 and Day 180 |