Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type II Diabetes Mellitus

Inclusion Criteria

• Diagnosed type II diabetes mellitus (according to WHO criteria, 1999 - 2006).
• Patient's age from 18 to 65 years inclusive.
• Level of glycosylated hemoglobin 7.0- 10.0 %.
• Dose of basal insulin ≥10 units/day combined with metformin or with metformin and sulfonylurea derivatives during not less than 3 months prior to inclusion in the trial.
• Body mass index ≥25.0 and ≤40.0kg/m^2.
• Constant body weight (without fluctuations > 10% during not less than 3 months prior to inclusion in the trial).
• Glomerular filtration rate ≥ 60 ml/ min/1.73m^2.
• Stable dose of basal insulin for the last 3 months.(Permissible fluctuations are ±10%.)
• Usage of contraceptive methods by both gender patients of reproductive age during the trial and within 30 days after ending the participation in the trial.
• Availability of signed patient information sheet (Informed Consent form) for participation in the clinical trial.

Exclusion Criteria

• Acute diabetes mellitus complications for 3 months prior to inclusion in the trial (diabetic ketoacidosis, hyperosmolar hyperglycemic state, lacticemia, severe hypoglycemia and hypoglycemic coma).
• Diabetic retinopathy, preproliferative, proliferative or terminal stages (based on the results of oculist examination during screening period or 6 months prior to the trial).
• Diabetic nephropathy, proteinuria stage, chronic kidney disease on 3, 4 or 5 stage.
• Diabetic microangiopathy:
• ishemic heart disease (medical history of a sudden coronary death with successful reanimation, medical history of myocardial infarction, stable exertional angina III or IV FC; unstable angina; postinfarction cardiosclerosis; chronic heart failure III or IV FC);
• cerebrovascular diseases (medical history of acute cerebrovascular accident; progressive vascular leukoencephalopathy; vascular dementia);
• chronic obliterative peripheral vascular diseases (clinically significant);
• diabetic neuroosteoarthropathy;
• diabetic foot (clinically significant).
• Heart rhythm disorder:
• II-III atrioventricular block;
• sick sinus syndrome;
• long QT interval syndrome;
• complete left bundle branch block;
• block of 2/3 bundle branches;
• WPW syndrome;
• ventricular arrhythmia of III grade according Laun-Wolf;
• paroxysmal supraventricular tachycardia;
• paroxysmal/recurrent ventricular tachycardia;
• atrial flutter and fibrillation;
• ventricular flutter and fibrillation;
• heart pacemaker implant.
• Uncontrolled arterial hypertension characterized by the following blood tension values: systolic blood pressure over 160 mm Hg and/or diastolic blood pressure over 100 mm Hg.
• Severe concomitant pathology including clinically significant cardio- vascular diseases of III - IV functional class (according to New York Heart Association classification, 1964), nervous and endocrine system diseases, including morbid obesity (body mass index≥40.0 kg/m^2), renal insufficiency, liver failure.
• Medical history of pancreatectomy or transplantation of pancreatic/islet cells.
• Medical history of renal transplantation.
• Malignant neoplasms/suspected malignant neoplasms.
• Exacerbations or decompensation of chronic diseases affecting a patient's ability to participate in the clinical trial.
• The results of analysis of liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than threefold exceeding of upper limit of normal values.
• Level of fasting triglycerides >5.64 mmol/L.
• Medical history of bariatric surgical operations.
• Medical history of polyvalent allergy
• Allergy/ intolerance to any of the components of medications used in the treatment.
• Intake of medicines listed in the section "Prohibited concomitant treatment" for 3 months prior to the inclusion in the trial.
• Pregnancy, breast-feeding.
• Drug addiction, alcohol usage in the amount exceeding 2 units of alcohol per day.
• Mental disorders of a patient.
• Night work.
• Participation in other cli