Poster Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

Once daily liraglutide (1.2mg) vs twice daily exenatide (10ug) in the treatment of type 2 diabetes patients: a meta-analysis. (#374)

Mirella Daja 1 , Beth O'Leary 2 , Sarah-Jane McKenna 2 , Michael Adena 3
  1. Novo Nordisk Pharmaceuticals Pty Ltd, Australia, Sydney, NSW, Australia
  2. Health Economics, Covance, Sydney, NSW, Australia
  3. Datalytics, Canberra, ACT, Australia

Liraglutide and exenatide are glucagon-like peptide-1 (GLP-1) receptor agonists approved for the treatment of type 2 diabetes. A randomised controlled trial (RCT) comparing 1.8mg liraglutide once daily (od) with exenatide 10ug twice daily (bid) found liraglutide provided a statistically superior HbA1c reduction with an estimated treatment difference of -0.33% [95% CI: -0.47 ; -0.18]1. As there are no head to head data comparing the efficacy and safety of 1.2mg liraglutide od with exenatide 10ug bid, an indirect comparison was performed.

A systematic literature search of databases (MEDLINE, EMBASE, CUCO, BIOSIS, PUBMED and the Cochrane Library) and trial registers (National Institutes of Health (NIH) and the Australian New Zealand Clinical Trials Registry (ANZCTR)) was conducted to identify all relevant RCTs of liraglutide 1.2mg od and exenatide 10ug bid. Three trials2-4 of liraglutide 1.2mg od vs placebo and 10 trials5-14 of exenatide 10ug bid versus placebo were identified allowing an indirect comparison with placebo as the common arm. No comparisons were possible using active treatments as the common arm.

Liraglutide 1.2mg od compared with exenatide 10μg bid showed statistically significantly better efficacy for HbA1c (mean difference -0.29% [-0.53, -0.05]) and FPG (mean difference -0.92mM [-1.43, -0.41]). Rates of withdrawal from the trials was significantly lower with liraglutide 1.2mg od (odds ratio 0.34 [0.22, 0.52]), while rates of adverse events (AEs) and hypoglycaemia were similar (odds ratio 0.83 [0.55, 1.25] and 0.78 [0.24, 2.55] respectively). Although a similar proportion of patients experienced nausea (odds ratio 0.81 [0.41, 1.61]), the mean duration of nausea was significantly shorter with liraglutide 1.2mg od (2.7 days) compared with exenatide 10ug bd (14.1 days) (p=0.002).

In conclusion, liraglutide 1.2mg od was statistically superior to exenatide 10μg bid in terms of glycaemic control with a reduced duration of nausea and a lower risk of withdrawal from treatment.


  1. Buse et al (2009) Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 374: 39-47
  2. Marre et al., 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
  3. Nauck et al., 2009 Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes. Diabetes Care 32; 84-90
  4. Zinman et al., 2009 Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met TZD). Diabetes Care 32:1224–1230,
  5. Apovian C.M. et al (2010). "Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes." Am J Med 123(5): 468 e469-417.
  6. Buse J.B. et al (2011). "Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial." Ann Intern Med 154(2): 103-112.
  7. Buse J.B. et al (2004). "Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes." Diabetes Care 27(11): 2628-2635.
  8. DeFronzo R.A. et al (2005). "Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes." Diabetes Care 28(5): 1092-1100.
  9. Derosa G. et al (2012). "Exenatide plus metformin compared with metformin alone on beta-cell function in patients with Type 2 diabetes." Diabet Med.
  10. Gao Y. et al. (2009). "Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a sulphonylurea." Diabetes Res Clin Pract 83(1): 69-76.
  11. Kendall D.M. et al. (2005). "Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea." Diabetes Care 28(5): 1083-1091.
  12. Liutkus J.J. et al. (2010). "A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin." Diabetes Obes Metab 12(12): 1058-1065.
  13. Moretto T.J. et al. (2008). "Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study." Clin Ther 30(8): 1448-1460.
  14. Zinman B. et al. (2007). "The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial." Ann Intern Med 146(7): 477-485.