Liraglutide Effect and Action in our Diabetes - LEAD-6

Jun 14, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novo Nordisk A/S
Date Published:
01/01/2009
Date Updated:
06/14/2009
Original Posted Date:
06/14/2009
References

Description:

The goal of the trial was to evaluate treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide compared with exenatide among patients with type 2 diabetes.

Hypothesis:

Liraglutide would be more effective in reducing glycated hemoglobin (HbA1c).

Study Design

  • Randomized
  • Parallel
  • Stratified

Patients Screened: 663
Patients Enrolled: 464
Mean Follow Up: 26 weeks
Mean Patient Age: 56 years
Female: 51%

Patient Populations:

  • Patients 18-80 years of age with type 2 diabetes
  • HbA1c 7-11%
  • BMI <45 kg/m2
  • On maximal doses of metformin, sulfonylurea, or both for at least 3 months

Exclusions:

  • Previous insulin treatment
  • Previous use of liraglutide or exenatide
  • Renal or liver dysfunction
  • Significant cardiovascular disease
  • Retinopathy or maculopathy requiring treatment
  • Uncontrolled hypertension
  • Cancer

Primary Endpoints:

  • Change in HbA1c from baseline to week 26

Secondary Endpoints:

  • Proportion of patients achieving HbA1c targets
  • Change in fasting plasma glucose
  • Change in 7-point plasma fasting glucose
  • Bodyweight
  • β-cell function
  • Glucagon
  • Blood pressure
  • Lipid profile

Drug/Procedures Used:

Patients with type 2 diabetes on maximal doses of metformin, sulfonylurea, or both were randomized to liraglutide 1.8 mg daily (n = 233) versus exenatide 10 µg twice daily (n = 231) for 26 weeks.

Concomitant Medications:

Patients remained on their maximal dose of metformin, sulfonylurea, or both during the study period.

Principal Findings:

Overall, 464 patients were randomized. There was no difference in baseline characteristics between the groups. In the liraglutide group, the mean age was 56 years, 51% were women, mean body mass index (BMI) was 33 kg/m2, mean HbA1c was 8.2%, and mean systolic blood pressure was 132 mm Hg.

The mean change in HbA1c was -1.12% in the liraglutide group versus -0.79% in the exenatide group (p < 0.0001). The proportion of patients who achieved an HbA1c <7.0% was 54% versus 43% (p = 0.0015) and weight loss was -3.24 kg versus -2.87 kg (p = NS), respectively, for liraglutide versus exenatide.

Serious adverse events were 5.1% versus 2.6% and severe adverse events were 7.2% versus 4.7%, respectively, for liraglutide versus exenatide.

Interpretation:

Among patients with type 2 diabetes, the use of liraglutide for 26 weeks was associated with improved glycemic control compared with exenatide. Liraglutide resulted in a greater reduction in mean HbA1c, and a greater proportion of patients who achieved target HbA1c levels. Weight loss was similar between the groups. Serious and severe adverse events appeared to be greater in the liraglutide group. Based on glycemic data from this trial, the use of liraglutide appears to be an alternative to exenatide for patients on maximal doses of metformin, sulfonylurea, or both; however, adverse events will need to be carefully monitored.

References:

Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;June 8:[Epub ahead of print].

Keywords: Incretins, Glycated Hemoglobin A, Venoms, Body Mass Index, Peptides, Weight Loss, Metformin, Glucagon-Like Peptide 1, Diabetes Mellitus, Type 2, Blood Pressure, Hypoglycemic Agents


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