GliRACo1: Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors
Study Details
Study Description
Brief Summary
Subjects treated with Canagliflozin, Dapagliflozin and Empagliflozin obtained improvement on blood pressure values, body weight and cardiovascular mortality but pathophysiological explanations of these effects are not yet known.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The pathophysiological explanations of the cardiovascular improvement of patients treated with SGLT2i are not yet known: osmotic diuresis and natriuresis, direct effects of weight reduction, increased in nitric oxide release, oxidative stress reduction, local renin-angiotensin-aldosterone system (RAAS) inhibition are the supposed mechanism. In the Literature the diuretic effect of SGLT2i therapy seems to be even stronger than thiazide or thiazide-like drugs. However, it is not defined the role of SGLT2i on antidiuretic function (RAAS, brain natriuretic peptide-BNP and antidiuretic hormone-ADH). Defining this relation could be important for:
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knowing effect of SGLT2i on RAAS (drugs interferences are important particularly during case detection of primary aldosteronism);
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discovering antidiuretic response to SGLT2i treatment and interactions between RAAS, BNP and ADH on the volume improvement induced by this new antidiabetic drugs.
In addition the aim of the study is to define effect of treatment on blood pressure and body composition.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Diabetic patients 30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin. |
Drug: SGLT2 inhibitor
Start of the treatment with SGLT2i.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Changes from baseline of antidiuretic function parameters (BNP) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Blood samples for BNP (pg/mL).
- Changes from baseline of antidiuretic function parameters (BNP) [90 days after starting SGLT2i therapy]
Blood samples for BNP (pg/mL).
- Changes from baseline of antidiuretic function parameters (vasopressin) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Blood samples for Copeptin (pmol/L).
- Changes from baseline of antidiuretic function parameters (vasopressin) [90 days after starting SGLT2i therapy]
Blood samples for Copeptin (pmol/L).
- Changes from baseline of antidiuretic function parameters (osmolality) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Samples for plasma osmolality (mOsm/Kg).
- Changes from baseline of antidiuretic function parameters (osmolality) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Samples for urinary osmolality (mOsm/Kg).
- Changes from baseline of antidiuretic function parameters (osmolality) [90 days after starting SGLT2i therapy]
Samples for plasma osmolality (mOsm/Kg).
- Changes from baseline of antidiuretic function parameters (osmolality) [90 days after starting SGLT2i therapy]
Samples for urinary osmolality (mOsm/Kg).
- Changes from baseline of antidiuretic function parameters (sodium balance) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Samples for serum sodium (mmol/L).
- Changes from baseline of antidiuretic function parameters (sodium balance) [90 days after starting SGLT2i therapy]
Samples for serum sodium (mmol/L).
- Changes from baseline of antidiuretic function parameters (sodium balance) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Samples for urinary sodium (mmol/L).
- Changes from baseline of antidiuretic function parameters (sodium balance) [90 days after starting SGLT2i therapy]
Samples for urinary sodium (mmol/L).
- Changes from baseline of antidiuretic function parameters (potassium balance) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Samples for serum potassium (mmol/L).
- Changes from baseline of antidiuretic function parameters (potassium balance) [90 days after starting SGLT2i therapy]
Samples for serum potassium (mmol/L).
- Changes from baseline of antidiuretic function parameters (potassium balance) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Samples for urinary potassium (mmol/L).
- Changes from baseline of antidiuretic function parameters (potassium balance) [90 days after starting SGLT2i therapy]
Samples for urinary potassium (mmol/L).
- Changes from baseline of renin-angiotensin-aldosterone system parameters (renin) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Blood samples for plasma renin activity (ng/mL/h).
- Changes from baseline of renin-angiotensin-aldosterone system parameters (renin) [90 days after starting SGLT2i therapy]
Blood samples for plasma renin activity (ng/mL/h).
- Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone) [Before starting SGLT2i and 30 days the starting SGLT2i therapy]
Blood samples for aldosterone (pg/mL).
- Long term changes from baseline of renin-angiotensin-aldosterone system parameters [90 days after starting SGLT2i therapy]
Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)
Secondary Outcome Measures
- Changes from baseline of blood pressure values (ABPM) [Before starting SGLT2i and 90 days after the starting]
Mean Systolic and Diastolic Blood Pressure (mmHg)
- Changes from baseline of body composition [Before starting SGLT2i and 90 days after the starting]
Variation of parameters of Bioelectrical Impedance Analysis (BIA)
- Changes in basal glicemic control [Before starting SGLT2i and 90 days after the starting]
Blood samples for basal glucose (mg/dL).
- Changes in long term glicemic control [Before starting SGLT2i and 90 days after the starting]
Blood samples for Glycated albumin (mmol/mol).
Eligibility Criteria
Criteria
Inclusion Criteria:
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diabetic patients;
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clinical indication to SGLT2i therapy.
Exclusion Criteria:
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signs and symptoms of poor glycemic control (polydipsia, polyuria and weight loss);
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HbA1c >10% or 86 mmol/mol;
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Body Mass Index (BMI) > 40 Kg/m2;
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personal history of primary and secondary aldosteronism;
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personal history of heart failure;
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personal history of acute kidney injury;
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personal history of chronic kidney disease;
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personal history of liver cirrhosis;
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personal history of protein-wasting syndrome;
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personal history of renin secreting tumor;
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personal history of diabetes insipidus;
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personal history of syndrome of inappropriate antidiuresis (SIAD);
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personal history of hypocortisolism and hypercortisolism;
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therapy with Angiotensin Converting Enzyme inhibitors;
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therapy with Angiotensin Receptor Blockers;
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therapy with renin inhibitors;
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therapy with beta-blockers;
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therapy with alfa2-receptors agonists;
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therapy with Calcium Channel Blockers;
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therapy with diuretics;
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therapy with mineralocorticoid receptor antagonists;
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therapy with non steroidal and steroidal anti-inflammatory drugs.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mauro Maccario | Torino | Piemonte | Italy | 10126 |
Sponsors and Collaborators
- University of Turin, Italy
Investigators
- Principal Investigator: Mauro M Maccario, MD, Endocrinology, Diabetology and Metabolism; University of Turin
- Study Chair: Ezio E Ghigo, MD, Endocrinology, Diabetology and Metabolism; University of Turin
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GliRACo 1