Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial

Lancet. 2009 Feb 7;373(9662):473-81. doi: 10.1016/S0140-6736(08)61246-5. Epub 2008 Sep 24.

Abstract

Background: New treatments for type 2 diabetes mellitus are needed to retain insulin-glucose coupling and lower the risk of weight gain and hypoglycaemia. We aimed to investigate the safety and efficacy of liraglutide as monotherapy for this disorder.

Methods: In a double-blind, double-dummy, active-control, parallel-group study, 746 patients with early type 2 diabetes were randomly assigned to once daily liraglutide (1.2 mg [n=251] or 1.8 mg [n=247]) or glimepiride 8 mg (n=248) for 52 weeks. The primary outcome was change in proportion of glycosylated haemoglobin (HbA(1c)). Analysis was done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NTC00294723.

Findings: At 52 weeks, HbA(1c) decreased by 0.51% (SD 1.20%) with glimepiride, compared with 0.84% (1.23%) with liraglutide 1.2 mg (difference -0.33%; 95% CI -0.53 to -0.13, p=0.0014) and 1.14% (1.24%) with liraglutide 1.8 mg (-0.62; -0.83 to -0.42, p<0.0001). Five patients in the liraglutide 1.2 mg, and one in 1.8 mg groups discontinued treatment because of vomiting, whereas none in the glimepiride group did so.

Interpretation: Liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and leads to greater reductions in HbA(1c), weight, hypoglycaemia, and blood pressure than does glimepiride.

Trial registration: ClinicalTrials.gov NCT00294723.

Publication types

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

MeSH terms

  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide
  • Male
  • Middle Aged
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • glimepiride
  • Liraglutide
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT00294723