The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes

Novo Nordisk

Status and phase: Completed; Phase 3

Conditions: Diabetes; Diabetes Mellitus, Type 2

Treatments: Drug: insulin detemir; Drug: liraglutide; Drug: metformin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00856986

2007-005317-19 (EudraCT Number)

NN2211-1842

Details and patient eligibility

About

This trial is conducted in Europe and North America. The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will continue their own pre-trial metformin treatment during the trial.

Enrollment: 987 patients

Sex: All

Ages: 18 to 84 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects diagnosed with type 2 diabetes, insulin naïve and treated with metformin as monotherapy for at least 3 months prior to screening, at a stable dose of at least 1500 mg/day or metformin (at least 1500 mg/day) and a sulfonylurea (less than or equal to half of the maximum approved dose), both at a stable dose for at least 3 months prior to screening. Previous short-term insulin treatment in connection with intercurrent illness is allowed at the discretion of the Investigator
• HbA1c 7.0-10.0% (both inclusive) for subjects on metformin monotherapy
• HbA1c 7.0-8.5% (both inclusive) for subjects on metformin in combination with a sulphonylurea

Exclusion criteria

• Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness at the discretion of the Investigator)
• Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 3 months prior to screening
• Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator
• Impaired kidney function
• Impaired liver function
• Uncontrolled treated/untreated hypertension
• Cancer or any clinically significant disease or disorder as judged by the Investigator
• Previous participation in the run-in phase of this trial. Re-screening is allowed once
• History of chronic pancreatitis or idiopathic pancreatitis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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987 participants in 5 patient groups

Lira 1.8

Experimental group

Description:

Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%

Treatment:

Drug: metformin

Drug: liraglutide

Insulin detemir + Lira 1.8

Experimental group

Description:

Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%

Treatment:

Drug: metformin

Drug: liraglutide

Drug: insulin detemir

Non-Randomised Lira 1.8

Experimental group

Description:

Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%

Treatment:

Drug: metformin

Drug: liraglutide

Early Withdrawals Lira 1.8

Other group

Description:

Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial

Treatment:

Drug: metformin

Drug: liraglutide

Intensified group

Other group

Description:

Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.

Treatment:

Drug: metformin

Drug: liraglutide

Drug: insulin detemir