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
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Changes from baseline of antidiuretic function parameters (vasopressin)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diabetic patients;
- •clinical indication to SGLT2i therapy.
排除标准
- •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.
研究组 & 干预措施
Diabetic patients
30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin.
干预措施: SGLT2 inhibitor (Drug)
结局指标
主要结局
Changes from baseline of antidiuretic function parameters (vasopressin)
时间窗: 90 days after starting SGLT2i therapy
Blood samples for Copeptin (pmol/L).
Changes from baseline of antidiuretic function parameters (sodium balance)
时间窗: 90 days after starting SGLT2i therapy
Samples for urinary sodium (mmol/L).
Changes from baseline of antidiuretic function parameters (BNP)
时间窗: 90 days after starting SGLT2i therapy
Blood samples for BNP (pg/mL).
Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone)
时间窗: 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)
时间窗: 90 days after starting SGLT2i therapy
Samples for urinary potassium (mmol/L).
Changes from baseline of antidiuretic function parameters (osmolality)
时间窗: 90 days after starting SGLT2i therapy
Samples for urinary osmolality (mOsm/Kg).
Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
时间窗: 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
时间窗: 90 days after starting SGLT2i therapy
Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)
次要结局
- Changes from baseline of body composition(Before starting SGLT2i and 90 days after the starting)
- Changes in basal glicemic control(Before starting SGLT2i and 90 days after the starting)
- Changes in long term glicemic control(Before starting SGLT2i and 90 days after the starting)
- Changes from baseline of blood pressure values (ABPM)(Before starting SGLT2i and 90 days after the starting)
研究者
Mauro Maccario
Medical Doctor, Professor
University of Turin, Italy