Type 2 diabetes Nutritional, Metabolic, Endocrine Non-insulin-dependent diabetes mellitus
Conditions
Interventions
1. Insulin detemir (Levemir)
2. Insulin Aspart (NovoRapid)
3. Biphasic Insulin Aspart (NovoMix30)
Sponsors
Novo Nordisk Limited (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 06/07/2007: 1. Informed consent 2. People with type 2 diabetes for at least 12 months who are insulin naive 3. On maximally tolerated metformin and sulphonylurea therapy for at least four months 4. Males and females, aged 18 years or more 5. Body mass index of 40.0 kg/m^2 or less 6. HbA1c in the range 7.0 to 10.0% inclusive 7. Able and willing to use insulin injections and perform self-monitoring of plasma glucose for the entire trial period Previous inclusion criteria: 1. 700 subjects with type 2 diabetes 2. Males and females 3. Aged 18 years or over 4. Body mass index (BMI) less than or equal to 40kg/m^2 currently treated with oral antidiabetic drugs (OADs) (metformin and/or a sulphonylurea) and with an HbA1c in the range 7.0% to 10.0% inclusive
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 06/07/2007: 1. Current or previous treatment with thiazolidinediones within the last six months 2. Current or previous treatment with an alpha-glucosidase inhibitor, repaglinide or nateglinide within the past 30 days 3. Oral Antidiabetic (OAD) treatment with three or more OADs within the last six months 4. Diabetes other than type 2 diabetes mellitus 5. Known sight-threatening retinopathy as judged by the investigator 6. Plasma creatinine 130 micromoles/l or more 7. Cardiac disease defined as: 7.1. Unstable angina pectoris within the last six months 7.2. Myocardial infarction (MI) within last six months 7.3. Congestive heart failure New York Heart Association (NYHA) class III and IV 8. Evidence of hepatic disease as determined by alanine aminotransferase (ALT) values of twice the upper limit of normal or more 9. Known hypoglycaemia unawareness or recurrent major hypoglycaemia as judged by the Investigator 10. Anticipated change in dose of concomitant medication, which may interfere with glucose regulation, such as monoamine oxidase inhibitors (MAOI), beta-adrenergic agents, anabolic steroids or systemic glucocorticoids 11. Uncontrolled hypertension with systolic blood pressure repeatedly 180 mmHg or more, or diastolic blood pressure 105 mmHg or more 12. Known or suspected allergy to trial products or related products 13. Any condition that the Investigator and/or the Sponsor feel would interfere with trial participation or the evaluation of results 14. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation 15. Pregnant or planning to become pregnant within the next 36 months, breastfeeding, or judged to be using inadequate contraceptive methods. Adequate contraceptive methods are sterilisation, intrauterine device (IUD), oral contraceptives or consistent use of barrier methods. 16. Receipt of any investigational trial drug within three months prior to participation in this trial 17. Subjects previously screened for participation or having already participated in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcomes measures as of 06/07/2007: The 4-T study will explore the efficacy and safety of treatment with biphasic, basal and prandial analogue insulin regimens in participants with type 2 diabetes mellitus (T2DM) inadequately controlled by two OADs. As this is an HbA1c treat-to-target study it is expected that the HbA1c levels in the three treatment groups will be similar but that there may be substantive differences in concomitant measures such as rates of hypoglycaemia, changes in weight and Quality of Life scores. Co-primary objective at one year: To compare the ability of three different single insulin formulation regimens to achieve good glycaemic control, defined as HbA1C levels less than or equal to 6.5 %, when added to current OAD treatment in subjects with inadequately controlled type 2 diabetes. Co-primary objective at three years: To determine the efficacy and durability of the three different insulin regimens in the longer term, and to assess the need for the addition of a second insulin formulation to achieve good glycaemic control. Co-primary objective at one year: To derive algorithms to estimate individual starting insulin dose requirements and insulin adjustment scales in populations such as this. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 06/07/2007: At one and three years, to compare the three treatment arms in terms of: 1. Proportions of participants who achieve HbA1c values less than or equal to 6.5% 2. Proportions who achieve HbA1c values of 6.5% or less without grade 2 (minor) or grade 3 (major) hypoglycaemia (as defined in the protocol) in the last four weeks of year one 3. Proportion who have clinically unacceptable hyperglycaemia (defined as two consecutive HbA1c values 8.0 % or more, or a single HbA1c value 10.0 % or more at or after 24 weeks) despite therapy with a single insulin formulation 4. The frequency of grade 1 (symptoms only), grade 2 (minor) or grade 3 (major) hypoglycaemia (as defined in the protocol) in a 24-hour period (00:00 - 24:00) 5. The frequency of grade 1, 2 or 3 nocturnal hypoglycaemia (23:00 - 05:59) 6. The frequency of grade 1, 2 or 3 daytime hypoglycaemia (06:00-22.59) 7. Changes in body weight 8. Changes in eight-point capillary plasma glucose profiles (self-measured) 9. Within-subject variation in pre-breakfast, pre-lunch and pre-dinner capillary plasma glucose levels (self-measured) 10. Changes in urinary albumin-to-creatinine ratio 11. Reasons for inability to achieve target HbA1c levels 12. Changes in quality of life and beliefs about medicines, both generic and disease-specific measures for people with diabetes treated with insulin | — |
Countries
Ireland, United Kingdom
Outcome results
None listed