Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin.
OBJECTIVE
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 µg weeks 1-2, then 20 µg; n = 77) or liraglutide QD (0.6 mg week 1, 1.2 mg week 2, then 1.8 mg; n = 71) 30 min 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 AUC(0:30-4:30h) : -12.6 vs. -4.0 h·mmol/L, respectively; p < 0.0001 (0:30 h = start of meal)]. Change in maximum PPG excursion was -3.9 mmol/l vs. -1.4 mmol/l, respectively (p < 0.0001). More lixisenatide-treated patients achieved 2-h PPG <7.8 mmol/l (69% vs. 29%). Changes in fasting plasma glucose were greater with liraglutide (-0.3 vs. -1.3 mmol/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 (-1.6 kg vs. -2.4 kg, 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.
Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, Neuss, Germany. christoph.kapitza@profil.com
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D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D006946:Hyperinsulinism / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000067758:Glucagon-Like Peptide-2 Receptor
D002096:C-Peptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D000069450:Liraglutide; D008687:Metformin; D010455:Peptides; C517652:hemoglobin A1c protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor