Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors

Study Overview
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Brief Summary
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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.

Detailed Description
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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: knowing effect of SGLT2i on RAAS (drugs interferences are important particularly during case detection of primary aldosteronism); 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.

Official Title
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Assessment of the Renin-angiotensin-aldosterone System (RAAS) and Antidiuretic Function in Patients With Type 2 Diabetes Before and During Treatment With Sodium-glucose Co-transporter 2 Inhibitors (SGLT2i): the GliRACo 1 Study

Conditions
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Diabetes Mellitus, Type 2, Arterial Hypertension, Body Weight Changes

Intervention / Treatment
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* Drug: SGLT2 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diabetic patients; clinical indication to SGLT2i therapy. Exclusion Criteria: signs and symptoms of poor glycemic control (polydipsia, polyuria and weight loss); HbA1c >10% or 86 mmol/mol; Body Mass Index (BMI) > 40 Kg/m2; personal history of primary and secondary aldosteronism; personal history of heart failure; personal history of acute kidney injury; personal history of chronic kidney disease; personal history of liver cirrhosis; personal history of protein-wasting syndrome; personal history of renin secreting tumor; personal history of diabetes insipidus; personal history of syndrome of inappropriate antidiuresis (SIAD); personal history of hypocortisolism and hypercortisolism; therapy with Angiotensin Converting Enzyme inhibitors; therapy with Angiotensin Receptor Blockers; therapy with renin inhibitors; therapy with beta-blockers; therapy with alfa2-receptors agonists; therapy with Calcium Channel Blockers; therapy with diuretics; therapy with mineralocorticoid receptor antagonists; therapy with non steroidal and steroidal anti-inflammatory drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diabetic patients<br>30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin. | Drug: SGLT2 inhibitor<br>* Start of the treatment with SGLT2i.<br>* Other names: Dapagliflozin, Empagliflozin, Canagliflozin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline of antidiuretic function parameters (BNP) | Blood samples for BNP (pg/mL). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (BNP) | Blood samples for BNP (pg/mL). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (vasopressin) | Blood samples for Copeptin (pmol/L). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (vasopressin) | Blood samples for Copeptin (pmol/L). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (osmolality) | Samples for plasma osmolality (mOsm/Kg). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (osmolality) | Samples for urinary osmolality (mOsm/Kg). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (osmolality) | Samples for plasma osmolality (mOsm/Kg). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (osmolality) | Samples for urinary osmolality (mOsm/Kg). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (sodium balance) | Samples for serum sodium (mmol/L). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (sodium balance) | Samples for serum sodium (mmol/L). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (sodium balance) | Samples for urinary sodium (mmol/L). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (sodium balance) | Samples for urinary sodium (mmol/L). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (potassium balance) | Samples for serum potassium (mmol/L). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (potassium balance) | Samples for serum potassium (mmol/L). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (potassium balance) | Samples for urinary potassium (mmol/L). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of antidiuretic function parameters (potassium balance) | Samples for urinary potassium (mmol/L). | 90 days after starting SGLT2i therapy | 
| Changes from baseline of renin-angiotensin-aldosterone system parameters (renin) | Blood samples for plasma renin activity (ng/mL/h). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Changes from baseline of renin-angiotensin-aldosterone system parameters (renin) | Blood samples for plasma renin activity (ng/mL/h). | 90 days after starting SGLT2i therapy | 
| Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone) | Blood samples for aldosterone (pg/mL). | Before starting SGLT2i and 30 days the starting SGLT2i therapy | 
| Long term changes from baseline of renin-angiotensin-aldosterone system parameters | Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL) | 90 days after starting SGLT2i therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline of blood pressure values (ABPM) | Mean Systolic and Diastolic Blood Pressure (mmHg) | Before starting SGLT2i and 90 days after the starting | 
| Changes from baseline of body composition | Variation of parameters of Bioelectrical Impedance Analysis (BIA) | Before starting SGLT2i and 90 days after the starting | 
| Changes in basal glicemic control | Blood samples for basal glucose (mg/dL). | Before starting SGLT2i and 90 days after the starting | 
| Changes in long term glicemic control | Blood samples for Glycated albumin (mmol/mol). | Before starting SGLT2i and 90 days after the starting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sodium-Glucose Transporter 2 Inhibitors, Renin-Angiotensin System, Vasopressin, Natriuretic Peptide, Brain, Blood Pressure, Body Composition, Diabetes Mellitus, Type 2