Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin

Aim Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin. Methods In this 28-day, randomized, open-label, parallel-group, multicentre study (NCT01175473), patients (mean HbA1c 7.3%) received subcutaneous lixisenatide QD (10 mu g weeks 1-2, then 20 mu g; n=77) or liraglutide QD (0.6mg week 1, 1.2mg week 2, then 1.8mg; n=71) 30min before breakfast. Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal. Results Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC0:30-4:30h: -12.6 vs. -4.0h center dot mmol/L, respectively; p<0.0001 (0:30h=start of meal)]. Change in maximum PPG excursion was -3.9mmol/l vs. -1.4mmol/l, respectively (p<0.0001). More lixisenatide-treated patients achieved 2-h PPG <7.8mmol/l (69% vs. 29%). Changes in fasting plasma glucose were greater with liraglutide (-0.3 vs. -1.3mmol/l, p<0.0001). Lixisenatide provided greater decreases in postprandial glucagon (p<0.05), insulin (p<0.0001) and C-peptide (p<0.0001). Mean HbA1c decreased in both treatment groups (from 7.2% to 6.9% with lixisenatide vs. 7.4% to 6.9% with liraglutide) as did body weight (-1.6kg vs. -2.4kg, respectively). Overall incidence of adverse events was lower with lixisenatide (55%) versus liraglutide (65%), with no serious events or hypoglycaemia reported. Conclusions Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG (AUC) during a morning test meal versus prebreakfast liraglutide. Lixisenatide provided significant decreases in postprandial insulin, C-peptide (vs. an increase with liraglutide) and glucagon, and better gastrointestinal tolerability than liraglutide.