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)

Diabetes Obes Metab. 2017 Sep;19(9):1252-1259. doi: 10.1111/dom.12945. Epub 2017 Apr 27.

Abstract

Aim: To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.

Materials and methods: 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.

Results: Lixisenatide reduced PPG exposure to a statistically significantly greater extent than sitagliptin: least squares (LS) mean change from baseline in PPG AUC0:00-4:00h was -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.

Conclusion: Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

Keywords: gastric emptying; glucagon-like peptide 1 receptor agonist; lixisenatide; postprandial glucose; randomized trial; type 2 diabetes mellitus.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Biomarkers / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance
  • Drug Therapy, Combination / adverse effects
  • Female
  • Follow-Up Studies
  • Gastric Emptying / drug effects
  • Glucagon-Like Peptide-1 Receptor / administration & dosage
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Subcutaneous
  • Insulin Glargine / adverse effects
  • Insulin Glargine / therapeutic use
  • Japan
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Postprandial Period
  • Sitagliptin Phosphate / adverse effects
  • Sitagliptin Phosphate / therapeutic use*

Substances

  • Biomarkers
  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • lixisenatide
  • Sitagliptin Phosphate
  • Glucagon-Like Peptide-1 Receptor Agonists

Associated data

  • ClinicalTrials.gov/NCT02200991