title: Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study).
abstract: To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.
  
  
  
  This multicentre, open-label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once-daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC0:00-4:00h]) from baseline to day 29.
  
  
  
  Lixisenatide reduced PPG exposure to a statistically significantly greater extent than sitagliptin: least squares (LS) mean change from baseline in PPG AUC0:00-4:00hwas -347.3 h·mg/dL (-19.3 h·mmol/L) in the lixisenatide group and -113.3 h·mg/dL (-6.3 h·mmol/L) in the sitagliptin group (LS mean between-group difference -234.0 h·mg/dL [-13.0 h·mmol/L], 95% confidence interval -285.02 to -183.00 h·mg/dL [-15.8 to -10.2 h·mmol/L]; P < .0001). Lixisenatide led to significantly greater LS mean reductions in maximum PPG excursion than sitagliptin (-122.4 vs -46.6 mg/dL [-6.8 vs -2.6 h·mmol/L]; P < .0001). Change-from-baseline reductions in exposure to C-peptide, fasting glycoalbumin levels, and the gastric emptying rate were greater in the lixisenatide than in the sitagliptin group. The incidence of treatment-emergent adverse events was higher with lixisenatide (60.9%) than with sitagliptin (16.4%), with no serious events or severe hypoglycaemia reported.
  
  
  
  Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.
authors.affiliation: Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine and Faculty of Medicine, Akita, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Medical Affairs, Sanofi K.K., Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Senda
authors.affiliation: Diabetes and Cardiovascular Medical Operations, Sanofi K.K., Tokyo, Japan.
authors.forename: Yusuke
authors.identifier: 0000-0001-8033-6708
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Diabetes and Cardiovascular Medical Operations, Sanofi K.K., Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Biostatistics and Programming, Sanofi K.K., Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.affiliation: Diabetes and Cardiovascular Medical Operations, Sanofi K.K., Tokyo, Japan.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Shuto
authors.affiliation: Department of General Medicine and Emergency Care, Toho University School of Medicine, Omori Hospital, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Urita
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005746:Gastric Emptying / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor / Q000008:administration & dosage / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D000069036:Insulin Glargine / Q000009:adverse effects / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019518:Postprandial Period; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D010455:Peptides; D000068900:Sitagliptin Phosphate; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: gastric emptying; glucagon-like peptide 1 receptor agonist; lixisenatide; postprandial glucose; randomized trial; type 2 diabetes mellitus