Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial

Diabetes Care. 2015 Jul;38(7):1263-73. doi: 10.2337/dc14-1984. Epub 2015 Apr 17.

Abstract

Objective: This mechanistic trial compared the pharmacodynamics and safety of lixisenatide and liraglutide in combination with optimized insulin glargine with/without metformin in type 2 diabetes (T2D).

Research design and methods: This was a multicenter, randomized, open-label, three-arm trial comparing lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg once daily for 8 weeks in combination with insulin glargine after optimized titration. The primary end point was change from baseline to week 8 in incremental area under the postprandial plasma glucose curve for 4 h after a standardized solid breakfast (AUC PPG0030-0430 h). Changes from baseline in gastric emptying, 24-h plasma glucose profile, HbA1c, fasting plasma glucose (FPG), 24-h ambulatory heart rate and blood pressure, amylase and lipase levels, and adverse events (AEs) were also assessed.

Results: In total, 142 patients were randomized and treated. Lixisenatide 20 µg achieved greater reductions of AUC PPG0030-0430 h compared with liraglutide (marginal mean [95% one-sided CI] treatment difference, -6.0 [-7.8] h ⋅ mmol/L [-108.3 (-140.0) h ⋅ mg/dL] vs. liraglutide 1.2 mg and -4.6 [-6.3] h ⋅ mmol/L [-83.0 (-114.2) h ⋅ mg/dL] vs. liraglutide 1.8 mg; P < 0.001 for both), and gastric emptying was delayed to a greater extent than with liraglutide 1.2 and 1.8 mg (P < 0.001 for treatment comparisons). FPG was unchanged in all treatment arms. At week 8, mean ± SD HbA1c was 6.2 ± 0.4% (44 ± 5 mmol/mol), 6.1 ± 0.3% (44 ± 4 mmol/mol), and 6.1 ± 0.3% (44 ± 4 mmol/mol) for lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg, respectively. At week 8, both liraglutide doses increased marginal mean ± SE 24-h heart rate from baseline by 9 ± 1 bpm vs. 3 ± 1 bpm with lixisenatide (P < 0.001). Occurrence of symptomatic hypoglycemia was higher with lixisenatide; gastrointestinal AEs were more common with liraglutide. Lipase levels were significantly increased from baseline with liraglutide 1.2 and 1.8 mg (marginal mean ± SE increase 21 ± 7 IU/L for both; P < 0.05).

Conclusions: Lixisenatide and liraglutide improved glycemic control in optimized insulin glargine-treated T2D albeit with contrasting mechanisms of action and differing safety profiles.

Trial registration: ClinicalTrials.gov NCT01596504.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Gastric Emptying / drug effects
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Glargine / administration & dosage
  • Liraglutide / administration & dosage*
  • Male
  • Metformin / administration & dosage
  • Middle Aged
  • Peptides / administration & dosage*
  • Postprandial Period / drug effects
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Insulin Glargine
  • lixisenatide
  • Liraglutide
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT01596504