Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin

Diabetes Obes Metab. 2013 Jul;15(7):642-9. doi: 10.1111/dom.12076. Epub 2013 Feb 25.

Abstract

Aim: 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.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Resistance
  • Female
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hyperinsulinism / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / administration & dosage
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Injections, Subcutaneous
  • Liraglutide
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*

Substances

  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Incretins
  • Peptides
  • hemoglobin A1c protein, human
  • lixisenatide
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT01175473