Study to Asses the Effect of Dapagliflozin on Central Blood Pressure Reduction.

IInstituto Gallego de Medicina Vascular

Status and phase: Unknown; Phase 4

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Dapagliflozin 10 mg; Drug: Glimepiride 4 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT02919059

ESR-14-10158

Details and patient eligibility

About

This superiority of central pressure versus peripheral measures to predict cardiovascular events has also been reported in general population or in elder people

Full description

The prognostic value of central systolic/diastolic pressure, central pulse pressure and AI has been well demonstrated, firstly after CAFÉ study, with 2073 hypertensive subjects followed up 3.4 years. It also evidenced higher prognostic value of central blood pressure compared to peripheral blood pressure. One year later, the STRONG study, showed central pulse pressure to be an independent cardiovascular risk factor as well as higher prognostic value compared to peripheral pulse pressure (Hazard ratio; 1,1510 mmHg Vs 1,10mmHg; X2: 13,4; p < 0,001). Those subjects with higher central blood pressure and central pulse pressure showed higher incidence of cardiovascular events. This superiority of central pressure versus peripheral measures to predict cardiovascular events has also been reported in general population or in elder people.

Finally, it has been also reported that dapagliflozin modestly reduces systolic blood pressure in patients with T2DM who were mostly receiving treatment for hypertension. Despite office blood pressure remains the gold standard method for screening, diagnostic and treatment of hypertension, it has been also well demonstrated that ambulatory blood pressure monitoring (ABPM) better estimates cardiovascular risk and target organ damage than office blood pressure. It still remains unclear the effects on 24 hours blood pressure reduction with SGLT-2 inhibitors.

The effects of SGLT2 inhibitors on central blood pressure reduction have not been documented.

Enrollment: 159 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• T2DM subjects with uncontrolled glycaemia, based on HbA1c levels (10% ≥ HbA1c ≥ 7%) at Visit 1.
• Patients may be treated for >3 months with a stable doses of metformin at optimal doses tolerated.
• Participants will be able to give and sign informed consent form.
• Age > 18 years of either gender.

Exclusion criteria

• Patients with two or more different oral antihyperglycemic agents.
• HbA 1c levels > 10%.
• Systolic BP >160 mm Hg and/or diastolic BP > 100 mm Hg before randomization.
• History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation or diabetes secondary to any condition.
• History of one or more severe hypoglycaemic episode within 6 months before screening.
• Myocardial infarction, unstable angina pectoris, congestive heart failure, life threatening arrhythmia, history of cerebrovascular accident within 3 months.
• Clinically relevant renal disease; defines if serum creatinine equal or lager than 1.5 mg/dl or eGFR < 60 ml/min/1.73m2, at screening.
• Liver function abnormal: glutamic-oxalacetic transaminase lager than 2 times of upper limit normal or glutamic-pyruvic transaminase lager than 2 times of upper limit normal
• Existence of any serious systemic disease
• Allergic history to the compounds of study medication
• Can not comply the study protocol or misunderstand the informed consent form
• Women of childbearing potential will be required to use a double-barrier method of birth control throughout study participation. Women who are surgically sterile or documented post-menopausal for at least 2 years are not considered to be of childbearing potential.
• Pregnant or breast-feeding or planning to become pregnant during the study.
• History of alcohol abuse (>350 g/week) within 3 years before screening.
• Concurrent therapy with medications that could be affect glycaemia (e.g. corticosteroids) or disallowed therapy (e.g. digoxin).
• Investigational drug treatment within the past 4 months
• Concomitant psychiatric diseases and/or habit/abuse of psychoactive substances
• Predictable lack of co-operation
• Shifts workers
• Employees of the investigator or study centre.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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159 participants in 2 patient groups

Dapagliflozin 10 mg

Experimental group

Description:

Dapagliflozin 10 mg once daily during 24 weeks

Treatment:

Drug: Dapagliflozin 10 mg

Glimepiride 4 mg

Active Comparator group

Description:

Glimepiride 4 mg once daily during 24 weeks

Treatment:

Drug: Glimepiride 4 mg