The trial was conducted in 76 office‐ or hospital‐based sites in Argentina, Canada, Finland, Germany, India, Mexico, the Netherlands, Serbia and the USA between 10 September 2012 and 22 October 2013. Protocol amendments occurring after the start of the study are described in Supplemental Data of File S1. Protocols, amendments and informed consent documents were approved by local independent ethics committees and the trial was conducted in accordance with Good Clinical Practice 24 and the Declaration of Helsinki 25 .
The study was registered withClinicalTrials.gov (identifier: NCT01617434).
The trial period was 29 weeks: 2 weeks of screening, 26 weeks of treatment and a 1‐week follow‐up period (Figure S1, File S1). Subjects were randomized 1 : 1 to receive a once‐daily dose of liraglutide 1.8 mg or placebo. Randomization was stratified according to screening HbA1c (≤8.0% vs >8.0%), metformin treatment (yes/no) and type of basal insulin analogue (insulin glargine vs insulin detemir). Liraglutide or placebo was initiated at the equivalent dose of 0.6 mg/day and the dose was increased in weekly increments of 0.6 mg to a final dose of 1.8 mg/day, which was then continued unchanged for the remainder of the study. The trial site personnel, subjects and sponsor remained blinded until trial completion.
The study medication (liraglutide or placebo) was injected subcutaneously once daily at a consistent time of day, and was added to the subject's stable pre‐study basal insulin analogue regimen ± metformin; before inclusion in the study, a subject's insulin dose had to remain stable for at least 8 weeks. For subjects with baseline HbA1c ≤8.0%, insulin dose was reduced by 20% at randomization to reduce the potential risk of hypoglycaemia. Up‐titration of insulin to no higher than the pre‐study dose was allowed during weeks 3–8. Otherwise, the insulin dose was kept at a stable, pre‐study dose level throughout the trial. Down‐titration was allowed for any subject at any time if there was a risk of hypoglycaemia (Tables S1–S3, File S1).
The study was registered with
The trial period was 29 weeks: 2 weeks of screening, 26 weeks of treatment and a 1‐week follow‐up period (Figure S1, File S1). Subjects were randomized 1 : 1 to receive a once‐daily dose of liraglutide 1.8 mg or placebo. Randomization was stratified according to screening HbA1c (≤8.0% vs >8.0%), metformin treatment (yes/no) and type of basal insulin analogue (insulin glargine vs insulin detemir). Liraglutide or placebo was initiated at the equivalent dose of 0.6 mg/day and the dose was increased in weekly increments of 0.6 mg to a final dose of 1.8 mg/day, which was then continued unchanged for the remainder of the study. The trial site personnel, subjects and sponsor remained blinded until trial completion.
The study medication (liraglutide or placebo) was injected subcutaneously once daily at a consistent time of day, and was added to the subject's stable pre‐study basal insulin analogue regimen ± metformin; before inclusion in the study, a subject's insulin dose had to remain stable for at least 8 weeks. For subjects with baseline HbA1c ≤8.0%, insulin dose was reduced by 20% at randomization to reduce the potential risk of hypoglycaemia. Up‐titration of insulin to no higher than the pre‐study dose was allowed during weeks 3–8. Otherwise, the insulin dose was kept at a stable, pre‐study dose level throughout the trial. Down‐titration was allowed for any subject at any time if there was a risk of hypoglycaemia (Tables S1–S3, File S1).
