Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes

• Published in: Diabetic medicine Vol. 22; no. 8; pp. 1016 - 1023
• Main Authors: Feinglos, M. N., Saad, M. F., Pi-Sunyer, F. X., An, B., Santiago, O.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2005; Blackwell
• Subjects: Adult; Aged; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Mass Index; Body Weight - drug effects; Delayed-Action Preparations; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; dose-response; Double-Blind Method; Drug Administration Schedule; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; GLP-1; Glucagon - administration & dosage; Glucagon - analogs & derivatives; Glucagon - therapeutic use; Glucagon-Like Peptide 1 - analogs & derivatives; Glycated Hemoglobin A - drug effects; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemic Agents - administration & dosage; Liraglutide; Male; Medical sciences; Middle Aged; secretagogue; weight; β-cell; Endocrinopathy; Type 2 diabetes; Human; GLP-1; Peptides; Body weight; Langerhans islet; Metabolic diseases; secretagogue; weight; β-cell; Dose activity relation; Regulation(control); dose-response; β Cell; Glycemia; Liraglutide; Endocrine pancreas
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2005.01567.x

Aims  Liraglutide (NN2211) is a long‐acting GLP‐1 analogue, with a pharmacokinetic profile suitable for once‐daily administration. This multicentre, double‐blind, parallel‐group, double‐dummy study explored the dose–response relationship of liraglutide effects on bodyweight and glycaemic control in subjects with Type 2 diabetes. Methods  Subjects (BMI 27–42 kg/m2) with Type 2 diabetes who were previously treated with an OAD (oral anti‐diabetic drug) monotherapy (69% with metformin), and had HbA1c ≤ 10% were enrolled. After a 4‐week metformin run‐in period, 210 subjects (27–73 years, 60% female) were randomised to receive liraglutide (0.045–0.75 mg) once daily or continued on metformin 1000 mg b.d. for 12 weeks. Results  Mean baseline values for the six treatment groups ranged from 6.8 to 7.5% for HbA1c, and 8.06–9.44 mmol/l (145–170 mg/dl) for fasting plasma glucose. After 12‐week treatment, a weight change of −0.05 to −1.9% was observed for the six treatment groups. Mean HbA1c changes from baseline for 0.045, 0.225, 0.45, 0.6, 0.75 mg liraglutide and metformin were +1.28%, +0.86%, +0.22%, +0.16%, +0.30% and +0.09%, respectively. No significant differences in HbA1c were observed between liraglutide and metformin groups at the three highest liraglutide dose levels (0.45, 0.6 and 0.75 mg). The lowest two liraglutide doses (0.045 mg and 0.225 mg) were not sufficient to maintain the fasting plasma glucose values achieved by metformin. No major hypoglycaemic episodes were reported. Episodes of nausea and/or vomiting were reported by 11 patients (6.3%) receiving liraglutide and three (8.8%) receiving metformin. Conclusions  Once‐daily liraglutide improved glycaemic control and weight, in a comparable degree to metformin. Liraglutide appeared to be safe and generally well tolerated. Higher doses of liraglutide merit study in future clinical trials.