Patients with type-2 diabetes treated with liraglutide had better glycaemic control over 26 weeks than those treated with exenatide in an open-label trial published in the Lancet.
Liraglutide and exenatide are glucagon-like peptide-1 (GLP-1) receptor agonists. GLP-1 is released by intestinal cells: it stimulates insulin secretion by the pancreas, slows intestinal motility, and promotes satiety. As these characteristics are potentially helpful in the treatment of type-2 diabetes, drugs that act via this pathway are of significant clinical interest. Exenatide is a GLP-1 agonist of animal origin that is currently in clinical use whereas liraglutide is an analogue of human GLP-1 in late stage development. This trial compared liraglutide with exenatide in patients with type-2 diabetes poorly controlled on maximal oral antidiabetic therapy.
Participants were adults with confirmed type-2 diabetes who were poorly controlled (glycated haemoglobin [HbA1c] level 7% to 11%) on maximal doses metformin, sulphonylurea, or both, for 3 months or more. Exclusion criteria included severe obesity (BMI 45 kg/m2 and above), previous long-term insulin treatment, and previous exposure to study drugs. They were randomised to liraglutide 1.8mg daily or exenatide 10microgm twice daily, both by s/c injection, reached after two weeks and four weeks respectively of dose escalation. Background oral antidiabetic therapy was continued, with up to 50% dose reduction of a sulphonylurea allowed if hypoglycaemia occurred. Study duration was 26 weeks from randomisation, and the primary outcome was change in HbA1c level from baseline to study end. Safety outcomes included hypoglycaemic episodes grouped as minor (could be self-treated) or major (third-party assistance needed to treat).
Of 663 patients screened, 464 were randomised, 233 to liraglutide and 231 to exenatide: 202 and 187 respectively completed the study, with nausea being the commonest reason for withdrawal. Three additional patients received study drugs without randomisation and were included in the safety but not efficacy analyses. Mean baseline HbA1c was 8.2% overall and over the course of the study it fell further in patients receiving liraglutide (by 1.2%) than in those receiving exenatide (by 0.79%) for an estimated treatment difference of −0.33% (95% CI −0.47 to −0.18; p<0.0001). p="0.0015)." p="0.0131).">
Lancet, published early online 8 June 2009; doi:10.1016/S0140-6736(09)60659-0 (link to abstract); Lancet, published early online 8 June 2009; doi:10.1016/S0140-6736(09)60942-9 (Comment; link to full text, access to subscribers only)