Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes.

Abstract

AIM:

Sulphonylureas (SUs) are often used as first-line treatments for type 2 diabetes in Japan, hence it is important to study new antidiabetic drugs in combination with SUs in Japanese patients.

METHODS:

The efficacy and safety of the once-daily human glucagon-like peptide-1 (GLP-1) analogue liraglutide were compared in 264 Japanese subjects [mean body mass index (BMI) 24.9 kg/m(2); mean glycated haemoglobin (HBA1c) 8.4%] randomized and exposed to receive liraglutide 0.6 mg/day (n = 88), 0.9 mg/day (n = 88) or placebo (n = 88) each added to SU monotherapy (glibenclamide, glicazide or glimeprimide) in a 24-week, double-blind, parallel-group trial.

RESULTS:

The mean change in HBA1c from baseline to week 24 (LOCF) was -1.56 (s.d. 0.84) and -1.46 (s.d. 0.95) with liraglutide 0.9 and 0.6 mg respectively, and -0.40 (s.d. 0.93) with placebo. HBA1c decreased in the placebo group from 8.45 to 8.06%, while liraglutide reduced HBA1c from 8.60 to 7.14%, and from 8.23 to 6.67% at the 0.6 and 0.9 mg doses respectively. Mean HBA1c at week 24 of the two liraglutide groups were significantly lower than the placebo group (p < 0.0001 for both). More subjects reached HBA1c < 7.0% with liraglutide (0.6 mg: 46.5%; 0.9 mg: 71.3%) vs. placebo (14.8%). Fasting plasma glucose (FPG) levels were significantly improved with liraglutide (difference -1.47 mmol/l and -1.80 mmol/l with 0.6 and 0.9 mg vs. placebo; p < 0.0001). Overall safety was similar between treatments: no major hypoglycaemic episodes were reported, while 84/77/38 minor hypoglycaemic episodes occurred in the 0.6 mg/0.9 mg and placebo treatment groups (all in combination with SU), reflecting lower ambient glucose levels. No relevant change in mean body weight occurred in subjects receiving liraglutide (0.6 mg: 0.06 kg; 0.9 mg: -0.37 kg), while mean body weight decreased in subjects receiving placebo (-1.12 kg).

CONCLUSIONS:

The addition of liraglutide to SU treatment for 24 weeks dose-dependently improved glycaemic control vs. SU monotherapy, without causing major hypoglycaemia or weight gain or loss.

• Authors: K Kaku, M F Rasmussen, P Clauson, Y Seino
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 12 Issue 4 Pg. 341-7 (Apr 2010) ISSN: 1463-1326 [Electronic] England
• PMID: 20380655 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Asian People
• Body Mass Index
• Body Weight
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination (methods)
• Female
• Glucagon-Like Peptide 1 (administration & dosage, analogs & derivatives)
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemic Agents (administration & dosage)
• Liraglutide
• Male
• Middle Aged
• Placebos
• Sulfonylurea Compounds (administration & dosage)
• Treatment Outcome