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.