title: 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.
abstract: OBJECTIVE
  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.
authors: Kansai Electric Power Hospital, Osaka, Japan.
authors: Y
authors: Y
authors: Seino
authors: A
authors: A
authors: Takami
authors: G
authors: G
authors: Boka
authors: E
authors: E
authors: Niemoeller
authors: D
authors: D
authors: Raccah
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007003:Hypoglycemia / 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; D007564:Japan; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D044465:White People; D055815:Young Adult; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D008687:Metformin; D010455:Peptides; D018027:Receptors, Glucagon; D013453:Sulfonylurea Compounds; C000593833:GLP1R protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: Caucasian; Japanese; lixisenatide; prandial; type 2 diabetes mellitus