Incretin-based therapies offer a new approach for the management of type 2 diabetes, with a mechanism of action distinct from any existing class of glucose-lowering agents. 1 These drugs improve the body's ability to control blood glucose by increasing active concentrations of glucagon-like peptide-1 (GLP-1). Two approaches have been used to enhance the action of GLP-1. First, incretin mimetics (exenatide) or analogues (liraglutide) act as agonists at the GLP-1 receptor to mimic the effect of endogenous GLP-1, but are resistant to degradation by dipeptidyl peptidase-4 (DPP-4). Second, drugs that specifically inhibit DPP-4 (sitagliptin, vildagliptin, saxagliptin) are used to increase the half-life of endogenous GLP-1 that is secreted in response to food intake. Both approaches have proven efficacy for reducing the concentration of glycosylated haemoglobin (HbA1c), without inducing severe hypoglycaemic episodes or promoting weight gain. 1 The drugs can be used alone or in combination with other oral glucose-lowering agents, such as metformin, sulphonylureas, andthiazolidinediones. Almost all published randomised trials of incretin therapies compared the new compound with a placebo or a reference glucose-lowering agent, but head-to-head comparisons between two incretin-based therapies are scarce. Onetrial compared 1.8 mg liraglutide once daily with 10 µg exenatide twice daily, and showed greater efficacy and better tolerance with liraglutide. 2 2 mg exenatide (longacting release) once weekly was more effective and bettertolerated than 10 µg exenatide twice daily. 3 No long-term comparisons of GLP-1 receptor agonists with DPP-4 inhibitors have been published, except in abstract form. 4 Therefore evidence is lacking to clearly position GLP-1 receptor agonists versus DPP-4 inhibitors after failure to manage type 2 diabetes with metformin. 5 Thus Richard Pratley and colleagues' 26-week, randomised, parallel-group, open-label trial, 6 published in The Lancet today, is of great interest. Added to metformin, 1.2 mg and 1.8 mg liraglutide once daily significantly improved blood glucose control (change in HbA1c from baseline: -1.24%, 95% Cl -1.37 to -1.11 for 1.2 mg; 1.50%, -1.63 to -1.37 for 1.8 mg) versus 100 mg sitagliptin once daily (-0.90%, -1.03 to -0.77; p<0.0001 for both comparisons). Furthermore, reductions in bodyweight were greater with 1.2 mg and 1.8 mg liraglutide (-2.86 kg, -3.39 to -2.32 for 1.2 mg; -3.38 kg, -3.91 to -2.84 for 1.8 mg) than with sitagliptin (-0.96 kg, -1.50 to -0.42; p<0.0001 for both comparisons). These results confirm previous reports of either liraglutide 2,7 or sitagliptin 8-10 in