Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

Diabetes Care. 2004 Jun;27(6):1335-42. doi: 10.2337/diacare.27.6.1335.

Abstract

Objective: Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients.

Research design and methods: A double-blind, randomized, parallel-group, placebo-controlled trial with an open-label comparator arm was conducted among 193 outpatients with type 2 diabetes. The mean age was 56.6 years and the mean HbA(1c) was 7.6% across the treatment groups. Patients were randomly assigned to one of five fixed-dosage groups of liraglutide (0.045, 0.225, 0.45, 0.60, or 0.75 mg), placebo, or open-label sulfonylurea (glimepiride, 1-4 mg). The primary end point was HbA(1c) after 12 weeks; secondary end points were fasting serum glucose, fasting C-peptide, fasting glucagon, fasting insulin, beta-cell function, body weight, adverse events, and hypoglycemic episodes.

Results: A total of 190 patients were included in the intention-to-treat (ITT) analysis. HbA(1c) decreased in all but the lowest liraglutide dosage group. In the 0.75-mg liraglutide group, HbA(1c) decreased by 0.75 percentage points (P < 0.0001) and fasting glucose decreased by 1.8 mmol/l (P = 0.0003) compared with placebo. Improvement in glycemic control was evident after 1 week. Body weight decreased by 1.2 kg in the 0.45-mg liraglutide group (P = 0.0184) compared with placebo. The proinsulin-to-insulin ratio decreased in the 0.75-mg liraglutide group (-0.18; P = 0.0244) compared with placebo. Patients treated with glimepiride had decreased HbA(1c) and fasting glucose, but slightly increased body weight. No safety issues were raised for liraglutide; observed adverse events were mild and transient.

Conclusions: A once-daily dose of liraglutide provides efficacious glycemic control and is not associated with weight gain. Adverse events with the drug are mild and transient, and the risk of hypoglycemia is negligible.

Publication types

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

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Body Weight / drug effects
  • Delayed-Action Preparations
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Glucagon / administration & dosage
  • Glucagon / analogs & derivatives*
  • Glucagon / therapeutic use*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Insulin / blood
  • Liraglutide
  • Male
  • Middle Aged
  • Placebos
  • Treatment Outcome

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Glycated Hemoglobin A
  • Insulin
  • Placebos
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Glucagon