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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
Author(s) -
Ahmann A.,
Rodbard H. W.,
Rosenstock J.,
Lahtela J. T.,
de Loredo L.,
Tornøe K.,
Boopalan A.,
Nauck M. A.
Publication year - 2015
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12539
Subject(s) - liraglutide , placebo , metformin , medicine , type 2 diabetes , endocrinology , insulin , clinical endpoint , nausea , basal (medicine) , diabetes mellitus , gastroenterology , urology , randomized controlled trial , alternative medicine , pathology
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 26 weeks, 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.