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Pharmacodynamics of the glucagon‐like peptide‐1 receptor agonist lixisenatide in Japanese and Caucasian patients with type 2 diabetes mellitus poorly controlled on sulphonylureas with/without metformin
Author(s) -
Seino Y.,
Takami A.,
Boka G.,
Niemoeller E.,
Raccah D.
Publication year - 2014
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.12276
Subject(s) - lixisenatide , metformin , medicine , postprandial , placebo , type 2 diabetes mellitus , diabetes mellitus , type 2 diabetes , endocrinology , pharmacodynamics , pharmacology , gastroenterology , pharmacokinetics , exenatide , alternative medicine , pathology
Aims The PDY6797 study evaluated efficacy, safety and pharmacodynamics of lixisenatide in Japanese and Caucasian patients with type 2 diabetes mellitus ( T2DM ) insufficiently controlled with sulphonylureas with/without metformin. Methods This randomized, double‐blind, placebo‐controlled trial comprised a single‐dose assessment of lixisenatide 5 and 10 µg, and a 5‐ to 6‐week repeated dose‐escalation assessment of lixisenatide 5 to 30 µg once ( QD ) or twice daily ( BID ). The primary endpoint was change in postprandial plasma glucose ( PPG ) area under the curve ( AUC ) [0:29–4:30 h] after a standardized breakfast at the highest tolerated lixisenatide dose. Change from baseline in glycated haemoglobin ( HbA1c ), 2‐h PPG and fasting plasma glucose ( FPG ) were assessed, as were adverse events. Results Change from baseline in PPG AUC [0:29–4:30 h] with lixisenatide QD and BID was significantly greater than placebo (p < 0.0001 for all study populations), with particularly prominent effects in Japanese patients. Greater reductions in PPG AUC [0:29–4:30 h] were seen with lixisenatide QD versus BID , while the totality of evidence suggested that the lixisenatide 20 µg dose was optimal. In the overall population, changes from baseline for 2‐h PPG , HbA1c and FPG were significant with lixisenatide QD and BID versus placebo (p < 0.01 for all). Lixisenatide was well tolerated. Conclusions Lixisenatide significantly reduced PPG AUC [0:29–4:30 h] versus placebo at the highest well‐tolerated dose in patients with T2DM treated with sulphonylureas with/without metformin and had a good safety and tolerability profile. Japanese patients experienced particular benefits with lixisenatide in terms of reductions in PPG excursions.