Effect of Different Insulin Administrations, All in Combination With Metformin, on Glycaemic Control in Subjects With Type 2 Diabetes Inadequately Controlled by Oral Anti-diabetic Drugs

Novo Nordisk

Status and phase: Completed; Phase 4

Conditions: Diabetes; Diabetes Mellitus, Type 2

Treatments: Drug: metformin; Drug: insulin detemir; Drug: biphasic insulin aspart 30; Drug: insulin aspart

Study type: Interventional

Funder types: Industry

Identifiers

NCT01068652

U1111-1112-6407 (Other Identifier)

INS-3782

Details and patient eligibility

About

This trial is conducted in Africa. The aim of this clinical trial is to investigate the effect of 50 weeks of treatment with different intensified insulin administrations (all in combination with a fixed dose of metformin) on blood sugar control in subjects with type 2 diabetes inadequately controlled by oral anti-diabetic drugs (OADs).

Enrollment: 403 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject)
• Diagnosed type 2 diabetes (WHO 1999 criteria)
• Currently treated with suboptimal daily dose of OADs (mono or combination therapy) for at least 6 months
• Male or female age at least 18 years old
• HbA1c at least 7.0 % and maximum 11.0% for subjects treated with metformin mono-therapy, or maximum 10% for subjects treated with OAD combination therapy
• BMI maximum 40 kg/m^2
• Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary
• Able and willing to be treated with up to 4 insulin injections per day

Exclusion criteria

• Known or suspected allergy to trial product(s) or related products
• Previous participation in this trial. Participation is defined as randomisation
• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)
• Participated in another clinical trial and received an investigational drug within the last weeks prior to the present trial
• Impaired hepatic function defined as alanine aminotransferase (ALT) or alkaline phosphatase (ALP) at least 2.5 times upper referenced limit
• Impaired renal function defined as serum-creatinine at least 1.3 mg/dL (at least 115 mmol/L) for males and at least 1.2 mg/dL (at least 106 mmol/L) for females
• Subject has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association class III and IV)
• Severe uncontrolled treated or untreated hypertension (sitting systolic blood pressure at least 180 mmHg or sitting diastolic blood pressure at least 100 mmHg)
• Proliferative retinopathy or macular oedema requiring acute treatment
• Metformin contraindications according to the package insert
• Current treatment with systemic corticosteroids
• Subject has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject
• Current addiction to alcohol or other addictive substances as determined by the Investigator
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation in the study or use of the glucose monitor
• History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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403 participants in 2 patient groups

Detemir + Met

Active Comparator group

Description:

Individually adjusted insulin detemir (Detemir) was given subcutaneoulsy (s.c.) at bedtime in the thigh at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, individually adjusted insulin aspart was added to the insulin detemir treatment (up to three doses daily for maximum 36 weeks, injected s.c. \[under the skin\]) if treatment target of HbA1c below 7.0% was not reached.

Treatment:

Drug: insulin detemir

Drug: insulin aspart

Drug: metformin

BIAsp 30 + Met

Active Comparator group

Description:

Individually adjusted biphasic insulin aspart 30 (BIAsp 30) was given subcutaneously (s.c.) in the abdomen at dinner at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, the dose was intensified up to 3 doses daily, injected s.c. (under the skin) if treatment target of HbA1c below 7.0% was not reached.

Treatment:

Drug: biphasic insulin aspart 30

Drug: metformin