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

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.

• Authors: Alan Garber, Robert Henry, Robert Ratner, Pedro A Garcia-Hernandez, Hiromi Rodriguez-Pattzi, Israel Olvera-Alvarez, Paula M Hale, Milan Zdravkovic, Bruce Bode, LEAD-3 (Mono) Study Group
• Journal: Lancet (London, England) (Lancet) Vol. 373 Issue 9662 Pg. 473-81 (Feb 07 2009) ISSN: 1474-547X [Electronic] England
• PMID: 18819705 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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