Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study.

Abstract

OBJECTIVE:

The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy.

RESEARCH DESIGN AND METHODS:

In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25-79 years) had type 2 diabetes, A1C of 7-11% (previous OAD monotherapy for > or =3 months) or 7-10% (previous OAD combination therapy for > or =3 months), and BMI < or =40 kg/m(2).

RESULTS:

A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8-2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide ( approximately 3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11-19% of the liraglutide-treated subjects versus 3-4% in the placebo and glimepiride groups. The incidence of nausea declined over time.

CONCLUSIONS:

In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.

• Authors: Michael Nauck, Anders Frid, Kjeld Hermansen, Nalini S Shah, Tsvetalina Tankova, Ismail H Mitha, Milan Zdravkovic, Maria Düring, David R Matthews, LEAD-2 Study Group
• Journal: Diabetes care (Diabetes Care) Vol. 32 Issue 1 Pg. 84-90 (Jan 2009) ISSN: 1935-5548 [Electronic] United States
• PMID: 18931095 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Glycated Hemoglobin A
• Hypoglycemic Agents
• Placebos
• Sulfonylurea Compounds
• glimepiride
• Liraglutide
• Glucagon-Like Peptide 1
• Metformin

Topics

• Adult
• Aged
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Drug Therapy, Combination
• Female
• Glucagon-Like Peptide 1 (analogs & derivatives, therapeutic use)
• Glycated Hemoglobin (drug effects, metabolism)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Liraglutide
• Male
• Metformin (therapeutic use)
• Middle Aged
• Obesity (complications)
• Placebos
• Safety
• Sulfonylurea Compounds (therapeutic use)