Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial

Aim: To confirm the superiority, compared with placebo, of adding liraglutide to pre-existing basal insulin analogue +/- metformin in adults with inadequately controlled type 2 diabetes [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)]. Methods: In this 26-week, double-blind, parallel-group study, conducted in clinics or hospitals, 451 subjects were randomized 1 : 1 to once-daily liraglutide 1.8 mg (dose escalated from 0.6 and 1.2 mg/day, respectively, for 1 week each; n = 226) or placebo (n = 225) added to their pre-existing basal insulin analogue (>= 20 U/day) +/- metformin (>= 1500 mg/day). After randomization, insulin adjustments above the pre-study dose were not allowed. The primary endpoint was HbA1c change. Results: After 26weeks, HbA1c decreased more with liraglutide [-1.3% (-14.2 mmol/mol)] than with placebo [-0.1% (-1.2 mmol/mol); p < 0.0001]. More subjects on liraglutide reached HbA1c targets: < 7.0% (59% vs 14%; p < 0.0001) and <= 6.5% (43% vs 4%; p < 0.0001) using slightly less insulin (35.8 IU vs 40.1 IU). Greater decreases from baseline (estimated treatment differences vs placebo; p < 0.0001) occurred in fasting plasma glucose (-1.3 mmol/l), seven-point glucose profiles (-1.6 mmol/l), body weight (-3.1 kg) and systolic blood pressure (-5.0 mmHg). Transient gastrointestinal adverse events (nausea: 22.2% vs 3.1%) and minor hypoglycaemia (18.2% vs 12.4%) were more frequent with liraglutide than placebo, and pulse increased (4.5 beats/min) compared with placebo. No severe hypoglycaemia or pancreatitis occurred. Conclusions: Adding liraglutide to a basal insulin analogue +/- metformin significantly improved glycaemic control, body weight and systolic blood pressure compared with placebo. Typical gastrointestinal symptoms and minor hypoglycaemia were more frequent with liraglutide.