Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU)

• Published in: Diabetic medicine Vol. 26; no. 3; pp. 268 - 278
• Main Authors: Marre, M., Shaw, J., Brändle, M., Bebakar, W. M. W., Kamaruddin, N. A., Strand, J., Zdravkovic, M., Le Thi, T. D., Colagiuri, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2009; Blackwell
• Subjects: Aged; Biological and medical sciences; Blood Glucose - drug effects; Body Weight - drug effects; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; dipeptidyl peptidase-4; Double-Blind Method; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - analogs & derivatives; glucagon-like peptide-1 receptor agonist; Humans; Hypoglycemia - blood; Hypoglycemia - drug therapy; Hypoglycemic Agents - administration & dosage; incretin; insulinotropic; Male; Medical sciences; Middle Aged; Original; Sulfonylurea Compounds - administration & dosage; thiazolidinedione; Thiazolidinediones - administration & dosage; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Incretin; Agonist; Body weight; Improvement; Hypoglycemic agent; Gastrointestinal hormone; glucagon-like peptide-1 receptor agonist; dipeptidyl peptidase-4; Lead; insulinotropic; Nutritional status; Human; thiazolidinedione; Enzyme; Nutrition disorder; Metabolic diseases; Corporal biometry; Thiazolidinedione derivatives; Heavy metal; Glucagon like peptide 1; Peptidases; Surveillance; Analog; Placebo; Rosiglitazone; Hydrolases; Daily dose; Endocrinology; Comparative study; Glycemia; Liraglutide
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/j.1464-5491.2009.02666.x

Aim  To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n ≥ 228) or placebo (n = 114) with glimepiride (2–4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes. Methods  In total, 1041 adults (mean ± sd), age 56 ± 10 years, weight 82 ± 17 kg and glycated haemoglobin (HbA1c) 8.4 ± 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose‐lowering mono : combination therapies (30 : 70%) to participate in a five‐arm, 26‐week, double‐dummy, randomized study. Results  Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA1c from baseline, (−1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (−0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (−0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [−2.5 to −2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (−0.4 mmol/l, P < 0.0001, baseline 12.7 mmol/l) or rosiglitazone (−1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (−0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (−0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (< 11%), vomiting (< 5%) and diarrhoea (< 8%). Conclusions  Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.