Phase 4 Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II Diabetic Subjects With Suboptimal Blood Pressure Control (GIANT)

Merck KGaA (EMD Serono)

Status and phase

Completed

Phase 4

Conditions

Diabetes Mellitus, Type II

Hypertension

Treatments

Drug: Bisoprolol

Study type

Interventional

Funder types

Industry

Identifiers

NCT01066039

EMR 200006-509

Details and patient eligibility

About

This is a 24-week, prospective, multicenter, open-label, single-arm study to assess the effect of bisoprolol on glycemic level in Type 2 diabetes mellitus (T2DM) controlled subjects with hypertension. The hypothesis of study is that there is no change in glycemic level and lipid metabolism as determined by glycosylated hemoglobin (HbA1c) using bisoprolol in T2DM subjects with suboptimal blood pressure (BP) control.

Full description

Diabetes mellitus and hypertension are two of the most common chronic conditions, and each predisposes to accelerated atherosclerosis, cardiovascular disease, and death. There has been a concern that beta-blocker might have adverse effects in subjects with diabetes on glucose metabolism, but some data shows that highly beta-1 selective agents such as bisoprolol are essentially free of metabolic disturbances involving blood sugar, insulin sensitivity and lipids.

This is a prospective, multicenter, single-arm, open-label study to assess the glycemic effect of bisoprolol in T2DM subjects with suboptimal BP control.

After pre-screening period, each enrolled subject with T2DM and suboptimal BP control will undergo laboratory test for efficacy and safety measurement. After that, subject will continue his/her usual dosage of antihypertensive medication and bisoprolol will be added.

Subjects will be instructed to continue their diet and level of physical activity and to attempt to maintain current body weight until completion of the study.

Bisoprolol will be titrated upward until a dosage that lowers BP to less than 130/80 millimeter of mercury (mmHg) during the first 2 months of treatment. The maximum dosage of bisoprolol will be 10 mg once daily. Following 6 month of added bisoprolol therapy, all efficacy and safety measurements will be repeated.

The duration of study will be up to 24 weeks for each subject.

Objectives

Primary objective:

To assess the effect of bisoprolol on glycemic control measured by change from baseline in HbA1c in T2DM subjects with suboptimal BP control

Secondary objectives:

To evaluate the effects of bisoprolol, as add-on therapy, on BP in T2DM subjects with suboptimal BP control
To evaluate the effects of bisoprolol, as add-on therapy, on insulin sensitivity as determined by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
To evaluate the effects of bisoprolol, as add-on therapy, on lipid metabolism as determined by lipid profile in T2DM subjects with suboptimal BP control
To evaluate the safety and tolerability of bisoprolol in T2DM subjects with suboptimal BP control
To assess the effects of bisoprolol combination therapy on insulin and c-peptide in T2DM subjects with suboptimal BP control compared to baseline
To assess the effects of bisoprolol combination therapy on microalbumin and albumin/creatinine ratio in T2DM subjects with suboptimal BP control compared to baseline

Enrollment

202 patients

Sex

All

Ages

20 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age of 20 years or older and less than 80 years
Subjects with T2DM
Subjects who have failed to achieve an appropriate BP level as a result of treatment with any antihypertensive drug other than beta blockers - that is, with BP inadequately controlled to greater than or equal to (>=) 130/80 mmHg. However, those who have used a beta blocker before 12 weeks can be enrolled
Subjects who underwent stable anti-diabetic regimen during the 12 weeks prior to screening
Signed written informed consent

Exclusion criteria

Ongoing insulin therapy
Change in two HbA1c levels measured at an interval of 4 weeks or longer for the previous 6 months is at least 1% (the last HbA1c is measured within 4 weeks)
Secondary hypertension
Subjects with renal impairment (creatinine greater than 150 micromol per liter or 1.7 milligram per deciliter)
Cardiovascular disease (uncontrolled or symptomatic arrhythmia, unstable angina, sick sinus syndrome, second or third degree atrioventricular (AV) block, bradycardia [less than 50 beats per minute], congestive heart failure, myocardial infarction, cerebral infraction attached within 12 weeks)
Subjects requiring BP control by at least 3 different antihypertensive drugs, or with either systolic blood pressure (SBP) >=180 mmHg or diastolic blood pressure (DBP) >=110 mmHg at baseline
Subjects with type 1 diabetes mellitus (T1DM)
Uncontrolled diabetes with HbA1c >9%
BMI >40 kilogram per square meter (kg/m^2)
Pulmonary disease (chronic obstructive pulmonary disease [COPD], bronchial asthma)
Other patients considered by the investigator to be not eligible for participation in this study for a legal or mental reason
Contraindications for beta-blocker
Pregnant or lactating women
Use of an investigational drug within 30 days of entry to the study