Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors

Not Applicable

• Conditions: Diabetes Mellitus, Type 2; Body Weight Changes; Arterial Hypertension
• Interventions: Drug: SGLT2 inhibitor

• Registration Number: NCT03917758
• Lead Sponsor: University of Turin, Italy

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.

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:

* 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.

Study Timeline

• Study Start: 2018-10-10
• Study First Submitted: 2019-04-07
• Study First Submitted QC: 2019-04-12
• Study First Posted: 2019-04-17
• Primary Completion: 2020-07-30
• Study Completion: 2020-10-30
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-02
• Last Update Posted: 2020-11-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diabetic patients	SGLT2 inhibitor	30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin.

Primary Outcome Measures

Name	Time	Method
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 (sodium balance)	90 days after starting SGLT2i therapy	Samples for urinary sodium (mmol/L).
Changes from baseline of antidiuretic function parameters (BNP)	90 days after starting SGLT2i therapy	Blood samples for BNP (pg/mL).
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).
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 antidiuretic function parameters (osmolality)	90 days after starting SGLT2i therapy	Samples for urinary osmolality (mOsm/Kg).
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	90 days after starting SGLT2i therapy	Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)

Secondary Outcome Measures

Name	Time	Method
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).
Changes from baseline of blood pressure values (ABPM)	Before starting SGLT2i and 90 days after the starting	Mean Systolic and Diastolic Blood Pressure (mmHg)

Trial Locations

Locations (1)

Mauro Maccario; 🇮🇹 Torino, Piemonte, Italy