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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)

  1. M. Marre,
  2. J. Shaw,
  3. M. Brändle,
  4. W. M. W. Bebakar,
  5. N. A. Kamaruddin,
  6. J. Strand,
  7. M. Zdravkovic,
  8. T. D. Le Thi,
  9. S. Colagiuri,
  10. on behalf of the LEAD-1 SU study group

Article first published online: 14 JAN 2009

DOI: 10.1111/j.1464-5491.2009.02666.x

Issue

Diabetic Medicine

Diabetic Medicine

Volume 26, Issue 3, pages 268–278, March 2009

Additional Information

How to Cite

Marre, M., Shaw, J., Brändle, M., Bebakar, W. M. W., Kamaruddin, N. A., Strand, J., Zdravkovic, M., Le Thi, T. D., Colagiuri, S. and on behalf of the LEAD-1 SU study group (2009), 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). Diabetic Medicine, 26: 268–278. doi: 10.1111/j.1464-5491.2009.02666.x

Author Information

  1. Service d’Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat—Claude Bernard, Paris, France, *International Diabetes Institute, Melbourne, Australia, †Division of Endocrinology, Diabetes and Osteology, Kantonsspital St Gallen, Switzerland, ‡Department of Medicine, Hospital Universiti Sains, Malaysia, Kelantan, §Department of Medicine, National University of Malaysia (UKM), Kuala Lumpur, Malaysia, ¶Oulun Diakonissalaitos, Oulu, Finland, **Novo Nordisk A/S, Bagsvaerd, Denmark and ††Institute of Obesity, Nutrition and Exercise, University of Sydney, Australia

* : Professor Michel Marre, Service d’Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat—Claude Bernard, 46 rue Henri Huchard, 75722 Paris Cedex 18, France. E-mail: michel.marre@bch.ap-hop-paris.fr

Publication History

  1. Issue published online: 12 MAR 2009
  2. Article first published online: 14 JAN 2009
  3. Accepted 20 December 2008

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Keywords:

  • dipeptidyl peptidase-4;
  • glucagon-like peptide-1 receptor agonist;
  • incretin;
  • insulinotropic;
  • thiazolidinedione

Abstract

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.

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