Medical Progress - Liraglutide vs exenatide for type 2 diabetes

Although 10 different classes of drug that reduce blood glucose levels are available, treatment of type 2 diabetes may still be unsatisfactory, and the development of new drugs might help. Glucagon-like peptide-1 (GLP-1), secreted by intestinal cells, stimulates insulin secretion and inhibits glucagon secretion in response to blood glucose levels. It also diminishes appetite and promotes proliferation of pancreatic beta cells. GLP-1 itself is rapidly degraded by dipeptidyl peptidase-4, but two types of drug have been developed; GLP-1 receptor agonists and human GLP-1 analogues resistant to the enzyme. Now liraglutide (an enzyme-resistant analogue of GLP-1) and exenatide (a GLP-1 receptor agonist) have been compared in a multinational trial.

A total of 264 adults with poorly controlled type 2 diabetes on maximum tolerated doses of metformin, a sulpho­nylurea or both were randomized to subcutaneous liraglutide 1.8 mg once daily or subcutaneous exenatide 10 µg twice daily for 26 weeks. Liraglutide caused signif­icantly greater reductions in HbA1c than did exenatide (from an overall mean baseline level of 8.2%, a mean reduction of 1.12% with liraglutide and 0.79% with exenatide). An HbA1c level of <7% was achieved by 54% versus 43%. The reduction in mean fasting plasma glucose was 1.61 versus 0.6 mmol/L. Weight loss was 3.24 kg versus 2.87 kg. Nausea and minor hypoglycaemia were both less frequent with liraglutide. Major hypoglycaemia occurred in two patients on a combination of exenatide and a sulphonylurea.

The results were better with liraglutide. Liraglutide might be suitable treatment when weight gain and hypoglycaemia are problems.

Buse JB, et al. 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 2009;374:39–47; De Block CEM, Van Gaal LF. GLP-1 receptor agonists for type 2 diabetes.